Symbol	Drug	Interaction type	Disease	Descent	Result	Mechanism	PMID	Details
IL6	IFN-b treatment	inhibitor	MS	N/A	IFN-b inhibits TNF-a, iNOS and IL-6 mRNA expression induced by IL-1/IFN-c. Pre- ()16 h), co- (0 h) and post-treatment (4 h) with IFN-b relative to the timing of IL-1/IFN-c addition show that pretreatment resulted in a greater inhibition of mRNA expression.	human fetal astrocytes revealed that IL-1-induced TNF-a, IL-6, as well as iNOS, are regulated by type-I and type-II IFNs.	12437583	Details
NOS2	IFN-b treatment	inhibitor	MS	N/A	IFN-b inhibits TNF-a, iNOS and IL-6 mRNA expression induced by IL-1/IFN-c. Pre- ()16 h), co- (0 h) and post-treatment (4 h) with IFN-b relative to the timing of IL-1/IFN-c addition show that pretreatment resulted in a greater inhibition of mRNA expression.	human fetal astrocytes revealed that IL-1-induced TNF-a, IL-6, as well as iNOS, are regulated by type-I and type-II IFNs.	12437583	Details
TNF	IFN-b treatment	inhibitor	MS	N/A	IFN-b inhibits TNF-a, iNOS and IL-6 mRNA expression induced by IL-1/IFN-c. Pre- ()16 h), co- (0 h) and post-treatment (4 h) with IFN-b relative to the timing of IL-1/IFN-c addition show that pretreatment resulted in a greater inhibition of mRNA expression.	human fetal astrocytes revealed that IL-1-induced TNF-a, IL-6, as well as iNOS, are regulated by type-I and type-II IFNs.	12437583	Details
IL1A	IFN-b treatment	activator	MS	N/A	Northern blot analysis for TNF-a, IL-6 and iNOS demonstrated that IFN-b enhanced mRNA expression induced by IL-1 alone.	human fetal astrocytes revealed that IL-1-induced TNF-a, IL-6, as well as iNOS, are regulated by type-I and type-II IFNs.	12437583	Details
Mbp	treatment with a peroxisome proliferator activated receptor-delta selective agonist and quetiapine	activator	EAE	CB57BL/6 mice	Furthermore, MBP-luci mice demonstrated enhanced luciferase signal and remyelination in the cuprizone model after treatment with a peroxisome proliferator activated receptor-delta selective agonist and quetiapine.	N/A	29806482	Details
CD40	IFN-b treatment	inhibitor	EAE	C57BL/6J mice	In these cells, IFN--induced CD40 mRNA expression was attenuated compared to wild-type (WT) microglia.	IFN-beta-induced SOCS-1 negatively regulates CD40 gene expression in macrophages and microglia	16571771	Details
Tnf	treatment with ORY-2001	inhibitor	EAE	SJL/J mice	only the treatment with ORY-2001 significantly reduced the levels of TNF-alpha and MCP-1.	This cytokine has an important role in initiating and limiting the extent and duration of immune-mediated inflammatory processes, organ damage, cell infiltration to the spinal cord, and demyelination.	35890315	Details
Ccl2	ORY-LSD1-treated	activator	EAE	SJL/J mice	On the other hand, the production of the anti-inflammatory cytokine IL-4 was increased with both treatments	chemokine	35890315	Details
Il4	treatment with ORY-2001	activator	EAE	SJL/J mice	On the other hand, the production of the anti-inflammatory cytokine IL-4 was increased with both treatments	cytokine	35890315	Details
Ifng	FTY720	inhibitor	EAE	SJL/J mice	while only FTY720 reduced the levels of IFNγ and increased IL-4 release in Con A-stimulated spleen cells	cytokine	35890315	Details
Il4	FTY720	activator	EAE	SJL/J mice	while only FTY720 reduced the levels of IFNγ and increased IL-4 release in Con A-stimulated spleen cells	cytokine	35890315	Details
Cxcl10	treatment with ORY-2001	activator	EAE	SJL/J mice	only the treatment with ORY-2001 resulted in a significant increase in the production of the pro-inflammatory chemokines IP-10 and MCP-1 induced by MOG35–55	chemokine	35890315	Details
Ccl2	treatment with ORY-2001	activator	EAE	SJL/J mice	only the treatment with ORY-2001 resulted in a significant increase in the production of the pro-inflammatory chemokines IP-10 and MCP-1 induced by MOG35–55	chemokine	35890315	Details
Irf1	treatment with MPA	inhibitor	EAE	AO rats	MPA markedly inhibited IFN-β LPS-triggered astrocyte expression of mRNA for iNOS and its transcription factor IRF-1.	IRF-1-dependent inhibition of iNOS activation might be partly responsible for the protective effect of MPA in EAE.	12203391	Details
Tnf	IFN-b treatment	inhibitor	N/A	C57Bl6/SJL	Analysis of the mechanisms leading to this attenuated inflammatory response showed a decrease in the serum levels of TNF-a and an inhibition of the activation of the transcription factor NF-kB in various tissues.	systemic administration of IFN-b might influence the response to pro-inflammatory stimuli, in particular through the antagonism of IFN-g signaling.	10845718	Details
NF-kB	IFN-b treatment	inhibitor	N/A	C57Bl6/SJL	Analysis of the mechanisms leading to this attenuated inflammatory response showed a decrease in the serum levels of TNF-a and an inhibition of the activation of the transcription factor NF-kB in various tissues.	systemic administration of IFN-b might influence the response to pro-inflammatory stimuli, in particular through the antagonism of IFN-g signaling.	10845718	Details
Timp1	treated with TNFα–dexamethasone	activator	N/A	Neonatal mice	Real-time RT-PCR analysis for TIMP-1 showed a 1.91 ± 0.08-fold increase in TIMP-1 expression for cells treated with TNFα–dexamethasone.	N/A	17317742	Details
Il17a	treated with rWJSC	inhibitor	EAE	C57BL/6 mice	The EAE mice treated with rWJSC showed reduction of Il-17, and brain lesions as well as brain cellular infiltration, in vivo.	gene therapy using anti-inflammatory cytokines can be a promising approach against multiple sclerosis (MS).	28836399	Details
Il4	using recombinant viruses	activator	EAE	C57BL/6 mice	WJSCs were transduced using recombinant viruses. IL-4, IL-10 and LIF overexpression were confirmed by ELISA, WB and qPCR.	gene therapy using anti-inflammatory cytokines can be a promising approach against multiple sclerosis (MS).	28836399	Details
Il10	using recombinant viruses	activator	EAE	C57BL/6 mice	WJSCs were transduced using recombinant viruses. IL-4, IL-10 and LIF overexpression were confirmed by ELISA, WB and qPCR.	gene therapy using anti-inflammatory cytokines can be a promising approach against multiple sclerosis (MS).	28836399	Details
Lif	using recombinant viruses	activator	EAE	C57BL/6 mice	WJSCs were transduced using recombinant viruses. IL-4, IL-10 and LIF overexpression were confirmed by ELISA, WB and qPCR.	gene therapy using anti-inflammatory cytokines can be a promising approach against multiple sclerosis (MS).	28836399	Details
Il6	treated with decitabine	inhibitor	EAE	C57BL/6 mice	Decitabine inhibits proinflammatory response of CNS in EAE mice.	N/A	28915632	Details
Cxcl10	treated with decitabine	inhibitor	EAE	C57BL/6 mice	Decitabine inhibits proinflammatory response of CNS in EAE mice.	N/A	28915632	Details
Ccl2	treated with decitabine	inhibitor	EAE	C57BL/6 mice	Decitabine inhibits proinflammatory response of CNS in EAE mice.	N/A	28915632	Details
Ccl4	treated with decitabine	inhibitor	EAE	C57BL/6 mice	Decitabine inhibits proinflammatory response of CNS in EAE mice.	N/A	28915632	Details
Ccl5	treated with decitabine	inhibitor	EAE	C57BL/6 mice	Decitabine inhibits proinflammatory response of CNS in EAE mice.	N/A	28915632	Details
Ccl17	treated with decitabine	inhibitor	EAE	C57BL/6 mice	Decitabine inhibits proinflammatory response of CNS in EAE mice.	N/A	28915632	Details
Ccl22	treated with decitabine	inhibitor	EAE	C57BL/6 mice	Decitabine inhibits proinflammatory response of CNS in EAE mice.	N/A	28915632	Details
Sirt1	MAT treatment	activator	EAE	Wistar rats	The expression of Sirtuin 1 (SIRT1), a member of an evolutionarily conserved gene family (sirtuins), was upregulated, as well as its downstream molecules Nrf2 and PGC-1α.	by activating SIRT1 to regulate PGC-1α and Nrf2, which, together, promote mitochondrial biosynthesis and reduce the oxidative stress of RGCs.	36238552	Details
Birc5	treated with YM155	inhibitor	N/A	C57BL/6 mice	In the cuYM group, the expression of BIRC5, BIRC4 and NAIP was reduced.	N/A	31489534	Details
Xiap	treated with YM155	inhibitor	N/A	C57BL/6 mice	In the cuYM group, the expression of BIRC5, BIRC4 and NAIP was reduced.	N/A	31489534	Details
Naip1	treated with YM155	inhibitor	N/A	C57BL/6 mice	In the cuYM group, the expression of BIRC5, BIRC4 and NAIP was reduced.	N/A	31489534	Details
Mbp	Sildenafil	inhibitor	N/A	rats	We found that sildenafil significantly diminished myelin gene expression and protein expression.	N/A	30849920	Details
LILRB1	IFN-β treatment	inhibitor	MS	227 mononuclear cell samples	Surprisingly, short-term IFN-β induced little shift in Th1/Th17/Th2 gene expression, but up-regulated immune-inhibitory genes(ILT, IDO1, PD-L1).	N/A	31648992	Details
LILRB4	IFN-β treatment	inhibitor	MS	227 mononuclear cell samples	Surprisingly, short-term IFN-β induced little shift in Th1/Th17/Th2 gene expression, but up-regulated immune-inhibitory genes(ILT, IDO1, PD-L1).	N/A	31648992	Details
LILRB2	IFN-β treatment	inhibitor	MS	227 mononuclear cell samples	Surprisingly, short-term IFN-β induced little shift in Th1/Th17/Th2 gene expression, but up-regulated immune-inhibitory genes(ILT, IDO1, PD-L1).	N/A	31648992	Details
LILRB3	IFN-β treatment	inhibitor	MS	227 mononuclear cell samples	Surprisingly, short-term IFN-β induced little shift in Th1/Th17/Th2 gene expression, but up-regulated immune-inhibitory genes(ILT, IDO1, PD-L1).	N/A	31648992	Details
IDO1	IFN-β treatment	inhibitor	MS	227 mononuclear cell samples	Surprisingly, short-term IFN-β induced little shift in Th1/Th17/Th2 gene expression, but up-regulated immune-inhibitory genes(ILT, IDO1, PD-L1).	N/A	31648992	Details
CD274	IFN-β treatment	inhibitor	MS	227 mononuclear cell samples	Surprisingly, short-term IFN-β induced little shift in Th1/Th17/Th2 gene expression, but up-regulated immune-inhibitory genes(ILT, IDO1, PD-L1).	N/A	31648992	Details
Sirt2	NSC-based gene therapy	activator	EAE	C57BL/6 mice	Moreover, differentiation of LINGO-1-Fc-producing NSCs into oligodendrocytes in vitro was largely diminished by an NAMPT inhibitor, indicating that LINGO-1-Fc enhances the NAMPT/NAD/Sirt2 pathway.	NAD then induces Sirt2, an endogenous neuroprotective factor that can promote OPC dif ferentiation.	27344330	Details
Nampt	NSC-based gene therapy	inhibitor	EAE	C57BL/6 mice	Moreover, differentiation of LINGO-1-Fc-producing NSCs into oligodendrocytes in vitro was largely diminished by an NAMPT inhibitor, indicating that LINGO-1-Fc enhances the NAMPT/NAD/Sirt2 pathway.	Through binding to the TrkB receptor, BDNF induces NAMPT, a rate-limiting enzyme involved in the conversion of nicotinamide into NAD.	27344330	Details
Calca	Gene therapy with CGRP-expressing mDC	activator	EAE	C57BL/6 mice	The CGRP mRNA expression was also markedly and significantly upregulated in CGRP-transfected mDCs compared with the mock-transfected cells	CGRP augmented the LPS and GM-CSF–induced IL-10 expression but suppressed the LPS and GM-CSF-induced IL-1 and IL-12 expression.	22807299	Details
Il10	Gene therapy with CGRP-expressing mDC	activator	EAE	C57BL/6 mice	These findings indicate that IL-10 production is upregulated in CGRP-transfected mDC.	Furthermore, neutralization of IL-10 activity largely abrogated the suppressive effects of CGRP on B7-2 upregulation.	22807299	Details
SOD2	melatonin treatment	activator	MS	Sina	whereas melatonin treatment caused a pronounced increase in MnSOD mRNA expression and activity only in patients.	It appears that the antioxidant status is affected in PBMCs from MS patients and melatonin could improve impaired antioxidant defense in MS through up egulation of SIRT1, MnSOD and catalase, which might be important in MS management.	26679105	Details
TNFSF10	interferon-beta therapy	activator	MS	N/A	Our results showed that in patients with multiple sclerosis, expression of both MxA and TRAIL in peripheral blood mononuclear cells increased significantly both in the immediate short term, and in the long term after treatment with interferon beta.	Our findings of an early and sustained induction of TRAIL expression in patients with multiple sclerosis responding to interferon-beta therapy now clearly shows that this ligand is involved in the immunoregulatory processes of this drug	12814715	Details
MX1	interferon-beta therapy	activator	MS	N/A	Our results showed that in patients with multiple sclerosis, expression of both MxA and TRAIL in peripheral blood mononuclear cells increased significantly both in the immediate short term, and in the long term after treatment with interferon beta.	N/A	12814715	Details
Tnf	IFN-β therapy	inhibitor	EAE	SJL/J mice	Furthermore, inhibition of the pro-inflammatory cytokines TNF-α, IFN-γ and IL-12 and enhanced expression of the anti inflammatory cytokines IL-10, IL-4 and TGF-β was observed in CNS tissue.	pro-inflammatory cytokines	18471898	Details
Ifng	IFN-β therapy	inhibitor	EAE	SJL/J mice	Furthermore, inhibition of the pro-inflammatory cytokines TNF-α, IFN-γ and IL-12 and enhanced expression of the anti inflammatory cytokines IL-10, IL-4 and TGF-β was observed in CNS tissue.	pro-inflammatory cytokines	18471898	Details
Il12a	IFN-β therapy	inhibitor	EAE	SJL/J mice	Furthermore, inhibition of the pro-inflammatory cytokines TNF-α, IFN-γ and IL-12 and enhanced expression of the anti inflammatory cytokines IL-10, IL-4 and TGF-β was observed in CNS tissue.	pro-inflammatory cytokines	18471898	Details
Il10	IFN-β therapy	activator	EAE	SJL/J mice	Furthermore, inhibition of the pro-inflammatory cytokines TNF-α, IFN-γ and IL-12 and enhanced expression of the anti inflammatory cytokines IL-10, IL-4 and TGF-β was observed in CNS tissue.	anti-inflammatory cytokines	18471898	Details
Il4	IFN-β therapy	activator	EAE	SJL/J mice	Furthermore, inhibition of the pro-inflammatory cytokines TNF-α, IFN-γ and IL-12 and enhanced expression of the anti inflammatory cytokines IL-10, IL-4 and TGF-β was observed in CNS tissue.	anti-inflammatory cytokines	18471898	Details
Tgfb1	IFN-β therapy	activator	EAE	SJL/J mice	Furthermore, inhibition of the pro-inflammatory cytokines TNF-α, IFN-γ and IL-12 and enhanced expression of the anti inflammatory cytokines IL-10, IL-4 and TGF-β was observed in CNS tissue.	anti-inflammatory cytokines	18471898	Details
Bdnf	IFN-β therapy	activator	EAE	SJL/J mice	In addition, mice receiving IFN-β had reduced apoptosis and increases in growth promoting factors including BDNF, CNTF, PDGF and VEGF.	growth factors	18471898	Details
Cntf	IFN-β therapy	activator	EAE	SJL/J mice	In addition, mice receiving IFN-β had reduced apoptosis and increases in growth promoting factors including BDNF, CNTF, PDGF and VEGF.	growth factors	18471898	Details
Pdgfa	IFN-β therapy	activator	EAE	SJL/J mice	In addition, mice receiving IFN-β had reduced apoptosis and increases in growth promoting factors including BDNF, CNTF, PDGF and VEGF.	growth factors	18471898	Details
Vegfa	IFN-β therapy	activator	EAE	SJL/J mice	In addition, mice receiving IFN-β had reduced apoptosis and increases in growth promoting factors including BDNF, CNTF, PDGF and VEGF.	growth factors	18471898	Details
MIR26A1	IFN-β therapy	activator	MS	N/A	MiR-26a-5p expression was significantly higher in IFN-β treated RRMS patients at 3 months treatment, keeping quite stable at 6 months treatments.	Functional annotations of hsa-mir-26a-5p targets revealed that several genes were implicated in Glutamate Receptor Signaling pathway, which is notoriously altered in neurodegenerative diseases as MS.	24885345	Details
CD80	Cladribine treatment	activator	MS	N/A	In addition, MDMs treated with cladribine showed increased expression of costimulatory molecules CD80 and CD40, as well as expression of anti-inflammatory, pro-trophic genes IL10 and MERTK, depending on the differentiation condition. Cladribine treatment in vitro.	N/A	35734180	Details
CD40	Cladribine treatment	activator	MS	N/A	In addition, MDMs treated with cladribine showed increased expression of costimulatory molecules CD80 and CD40, as well as expression of anti-inflammatory, pro-trophic genes IL10 and MERTK, depending on the differentiation condition. Cladribine treatment in vitro.	the costimulatory molecule CD40 as markers of proinflammatory activation	35734180	Details
IL10	Cladribine treatment	activator	MS	N/A	In addition, MDMs treated with cladribine showed increased expression of costimulatory molecules CD80 and CD40, as well as expression of anti-inflammatory, pro-trophic genes IL10 and MERTK, depending on the differentiation condition. Cladribine treatment in vitro.	anti-inflammatory cytokine	35734180	Details
MERIK	Cladribine treatment	activator	MS	N/A	In addition, MDMs treated with cladribine showed increased expression of costimulatory molecules CD80 and CD40, as well as expression of anti-inflammatory, pro-trophic genes IL10 and MERTK, depending on the differentiation condition. Cladribine treatment in vitro.	the efferocytosis-related receptor	35734180	Details
TGFB2	vitamin D treatment	activator	MS	N/A	Expression of TGF-β2 mRNA increased 2.84-fold	TGF-β2 inhibits macrophage inflammatory responses	26037400	Details
Tgfb1	Treatment with Abs	inhibitor	EAE	N/A	Treatment with Abs to CD8+ cells abrogates peptide-induced TGF-P mRNA expression, and aggravates disease in strains with the class I A' allele.	N/A	7522259	Details
Ifng	tolerance-promoting DNA vaccination focused to dendritic cells	inhibitor	EAE	C57BL/6 mice	Spleen cells derived from mice vaccinated with MOG- and cytokine-encoding plasmids show attenuated proliferation and IL-17/IFN- production in response to restimulation.	N/A	29408931	Details
Il17a	tolerance-promoting DNA vaccination focused to dendritic cells	inhibitor	EAE	C57BL/6 mice	Spleen cells derived from mice vaccinated with MOG- and cytokine-encoding plasmids show attenuated proliferation and IL-17/IFN- production in response to restimulation.	N/A	29408931	Details
CCL27	IFN-β1b-treated	activator	MS	N/A	A significant decrease was observed in the serum level of CCL27 in treatment-nave patients and IFN-β1b-treated patients compared to the healthy controls.	CCL27 is a novel chemokine	31935737	Details
H2	IFN-g treated	activator	EAE	N/A	IFN-g treated astrocytes up-regulated MHC-II expression levels after co-culture in the presence of MOG35–55-specific lymphocytes	N/A	23121666	Details
IL17A	IFN-β therapy	inhibitor	MS	RRMS	Th17 cells and plasma levels of IL-17A decreased in RRMS patients after IFN-β therapy.	N/A	34808619	Details
MX1	IFN-β therapy	activator	MS	RRMS	MxA gene expression was significantly induced upon IFN-β therapy in patients with RRMS.	Myxovirus resistance protein 1 (MxA) as one of the main reliable biomarkers for IFN-β bioactivity is measured upon treatment with IFN-β.	34808619	Details
BE	LDN treatment	activator	MS	PPMS	A significant (P < 0.05) increase of BE concentration(mean ± SEM) was measured either at 3 months(63.4 ± 4.8) and 6 months (76.9 ± 3.3) after the beginning of LDN treatment.	BE is a peptide neurotransmitter produced by pituitary and hypothalamic neuronal cells	18728058	Details
IL17A	treatment of ATRA	inhibitor	MS	RRMS	The results showed that single treatment of ATRA (p = 0.05) could significantly decrease the expression of IL-17 gene.	N/A	29155646	Details
RORC	treatment of DHA	inhibitor	MS	RRMS	single treatment of ATRA (p = 0.04) and single treatment of DHA (p = 0.05) induced significant inhibition on the expression of RORγt gene.	N/A	29155646	Details
IL17A	combined treatment with ATRA and DHA	inhibitor	MS	RRMS	The suppressive effect of combined treatment with ATRA and DHA on IL-17 (p = 0.02) and RORγt (p = 0.01) was also found significant showing that the combined treatments can have additive effects.	N/A	29155646	Details
RORC	combined treatment with ATRA and DHA	inhibitor	MS	RRMS	The suppressive effect of combined treatment with ATRA and DHA on IL-17 (p = 0.02) and RORγt (p = 0.01) was also found significant showing that the combined treatments can have additive effects.	N/A	29155646	Details
Ifng	IFN-β	inhibitor	EAE	N/A	TGF-b inhibits IEN-y secretion by MBP-activated spleen cells from Lewis rats with acute EAE as measured by ELISA.	N/A	8950703	Details
CD86	MMF treatment	inhibitor	MS	N/A	MMF treatment induced a less mature phenotype of mDCs with reduced expression of major histocompatibility complex class II (MHC-II), co-stimulatory molecules CD86, CD40, CD83, and expression of nuclear factor κB (NF-κB) subunits RELA and RELB.	N/A	29106333	Details
CD40	MMF treatment	inhibitor	MS	N/A	MMF treatment induced a less mature phenotype of mDCs with reduced expression of major histocompatibility complex class II (MHC-II), co-stimulatory molecules CD86, CD40, CD83, and expression of nuclear factor κB (NF-κB) subunits RELA and RELB.	N/A	29106333	Details
CD83	MMF treatment	inhibitor	MS	N/A	MMF treatment induced a less mature phenotype of mDCs with reduced expression of major histocompatibility complex class II (MHC-II), co-stimulatory molecules CD86, CD40, CD83, and expression of nuclear factor κB (NF-κB) subunits RELA and RELB.	N/A	29106333	Details
HLA-DRB1	MMF treatment	inhibitor	MS	N/A	MMF treatment induced a less mature phenotype of mDCs with reduced expression of major histocompatibility complex class II (MHC-II), co-stimulatory molecules CD86, CD40, CD83, and expression of nuclear factor κB (NF-κB) subunits RELA and RELB.	N/A	29106333	Details
RELA	MMF treatment	inhibitor	MS	N/A	MMF treatment induced a less mature phenotype of mDCs with reduced expression of major histocompatibility complex class II (MHC-II), co-stimulatory molecules CD86, CD40, CD83, and expression of nuclear factor κB (NF-κB) subunits RELA and RELB.	N/A	29106333	Details
RELB	MMF treatment	inhibitor	MS	N/A	MMF treatment induced a less mature phenotype of mDCs with reduced expression of major histocompatibility complex class II (MHC-II), co-stimulatory molecules CD86, CD40, CD83, and expression of nuclear factor κB (NF-κB) subunits RELA and RELB.	N/A	29106333	Details
CD86	DMF treatment	inhibitor	MS	N/A	MMF treatment induced a less mature phenotype of mDCs with reduced expression of major histocompatibility complex class II (MHC-II), co-stimulatory molecules CD86, CD40, CD83, and expression of nuclear factor κB (NF-κB) subunits RELA and RELB.	N/A	29106333	Details
CD40	DMF treatment	inhibitor	MS	N/A	MMF treatment induced a less mature phenotype of mDCs with reduced expression of major histocompatibility complex class II (MHC-II), co-stimulatory molecules CD86, CD40, CD83, and expression of nuclear factor κB (NF-κB) subunits RELA and RELB.	N/A	29106333	Details
CD83	DMF treatment	inhibitor	MS	N/A	MMF treatment induced a less mature phenotype of mDCs with reduced expression of major histocompatibility complex class II (MHC-II), co-stimulatory molecules CD86, CD40, CD83, and expression of nuclear factor κB (NF-κB) subunits RELA and RELB.	N/A	29106333	Details
HLA-DRB1	DMF treatment	inhibitor	MS	N/A	MMF treatment induced a less mature phenotype of mDCs with reduced expression of major histocompatibility complex class II (MHC-II), co-stimulatory molecules CD86, CD40, CD83, and expression of nuclear factor κB (NF-κB) subunits RELA and RELB.	N/A	29106333	Details
RELA	DMF treatment	inhibitor	MS	N/A	MMF treatment induced a less mature phenotype of mDCs with reduced expression of major histocompatibility complex class II (MHC-II), co-stimulatory molecules CD86, CD40, CD83, and expression of nuclear factor κB (NF-κB) subunits RELA and RELB.	N/A	29106333	Details
RELB	DMF treatment	inhibitor	MS	N/A	MMF treatment induced a less mature phenotype of mDCs with reduced expression of major histocompatibility complex class II (MHC-II), co-stimulatory molecules CD86, CD40, CD83, and expression of nuclear factor κB (NF-κB) subunits RELA and RELB.	N/A	29106333	Details
IFNG	MMF treatment	inhibitor	MS	N/A	T cells co-cultured with MMF-treated mDCs showed reduced proliferation with decreased production of interferon gamma (IFN-γ), interleukin-17 (IL-17), and granulocyte-macrophage colony-stimulating factor (GM-CSF) compared to untreated cells.	N/A	29106333	Details
IL17A	MMF treatment	inhibitor	MS	N/A	T cells co-cultured with MMF-treated mDCs showed reduced proliferation with decreased production of interferon gamma (IFN-γ), interleukin-17 (IL-17), and granulocyte-macrophage colony-stimulating factor (GM-CSF) compared to untreated cells.	N/A	29106333	Details
GM-CSF	MMF treatment	inhibitor	MS	N/A	T cells co-cultured with MMF-treated mDCs showed reduced proliferation with decreased production of interferon gamma (IFN-γ), interleukin-17 (IL-17), and granulocyte-macrophage colony-stimulating factor (GM-CSF) compared to untreated cells.	N/A	29106333	Details
Il4	treated with PBS or AdIF	activator	EAE	C57BL/6 mice	Those derived from AdIF-treated mice demonstrated increased IL-4 and suppressed IFN-γ secretion.	The newly discovered molecule AdIF may also render auto reactive T cells susceptible to the induction of apoptotic cell death.	21277028	Details
Ifng	treated with PBS or AdIF	inhibitor	EAE	C57BL/6 mice	Those derived from AdIF-treated mice demonstrated increased IL-4 and suppressed IFN-γ secretion.	The newly discovered molecule AdIF may also render auto reactive T cells susceptible to the induction of apoptotic cell death.	21277028	Details
Gfap	AST treatment	inhibitor	EAE	C57BL/6 mice	AST inhibited GFAP mRNA expression.	After AST treatment, the activation of astrocytes and microglia cells was inhibited as the mRNA levels of both GFAP and CD11b were reduced remarkably.	25150364	Details
Itgam	AST treatment	inhibitor	EAE	C57BL/6 mice	AST reduced CD11b mRNA expression.	After AST treatment, the activation of astrocytes and microglia cells was inhibited as the mRNA levels of both GFAP and CD11b were reduced remarkably.	25150364	Details
Nos2	AST treatment	inhibitor	EAE	C57BL/6 mice	AST prevented iNOS mRNA expression.	After AST treatment, the activation of astrocytes and microglia cells was inhibited as the mRNA levels of both GFAP and CD11b were reduced remarkably.	25150364	Details
Rorc	AST treatment	inhibitor	EAE	C57BL/6 mice	AST inhibited RORγt mRNA expression.	In our experiments, all of the three transcriptional factors were modulated by AST administra tion at mRNA levels.	25150364	Details
Tbx21	AST treatment	activator	EAE	C57BL/6 mice	AST increased T-bet mRNA expression.	In our experiments, all of the three transcriptional factors were modulated by AST administra tion at mRNA levels.	25150364	Details
Foxp3	AST treatment	activator	EAE	C57BL/6 mice	AST elevated Foxp3 mRNA expression.	In our experiments, all of the three transcriptional factors were modulated by AST administra tion at mRNA levels.	25150364	Details
Trp53	AST treatment	inhibitor	EAE	C57BL/6 mice	Compared with EAE mice without any treatment, protein expression of GFAP and p53 in AST treated EAE mice were inhibited remarkably(p < 0.05).	p53 plays a suppressive role in the inflammatory re sponse by regulation the cytokine profile as well as the destiny of infiltrated cells.	25150364	Details
Ifng	AST treatment	inhibitor	EAE	C57BL/6 mice	However, it decreased IFNγ (p < 0.01), TNFα (p < 0.01) and IL6 (p < 0.05) levels.	Deficiency of p53 increases the severity of EAE possibly by elongating the survival of inflammatory cells in the CNS, therefore, enhancing the production of pro inflammatory cytokines such as IL-6, TNF-α and IFN-γ.	25150364	Details
Tnf	AST treatment	inhibitor	EAE	C57BL/6 mice	However, it decreased IFNγ (p < 0.01), TNFα (p < 0.01) and IL6 (p < 0.05) levels.	Deficiency of p53 increases the severity of EAE possibly by elongating the survival of inflammatory cells in the CNS, therefore, enhancing the production of pro inflammatory cytokines such as IL-6, TNF-α and IFN-γ.	25150364	Details
Il6	AST treatment	inhibitor	EAE	C57BL/6 mice	However, it decreased IFNγ (p < 0.01), TNFα (p < 0.01) and IL6 (p < 0.05) levels.	Deficiency of p53 increases the severity of EAE possibly by elongating the survival of inflammatory cells in the CNS, therefore, enhancing the production of pro inflammatory cytokines such as IL-6, TNF-α and IFN-γ.	25150364	Details
Il6	Human adipose-derived mesenchymal stem cells	inhibitor	EAE	C57BL/6 mice	In the presence of Adi-IL-10-MSCs, Adi-eGFP-MSCs or their CM however, IL-6, IL-12p40, and TNF-a secretion was significant reduced.	This protective effect was associated with several anti inflammatory response mechanisms, including a reduction in peripheral T-cell proliferative responses, a decrease in pro inflammatory cytokine secretion as well as a preferential inhibition of Th17-mediated neuroinflammation.	23369732	Details
Il12b	Human adipose-derived mesenchymal stem cells	inhibitor	EAE	C57BL/6 mice	In the presence of Adi-IL-10-MSCs, Adi-eGFP-MSCs or their CM however, IL-6, IL-12p40, and TNF-a secretion was significant reduced.	This protective effect was associated with several anti inflammatory response mechanisms, including a reduction in peripheral T-cell proliferative responses, a decrease in pro inflammatory cytokine secretion as well as a preferential inhibition of Th17-mediated neuroinflammation.	23369732	Details
Tnf	Human adipose-derived mesenchymal stem cells	inhibitor	EAE	C57BL/6 mice	In the presence of Adi-IL-10-MSCs, Adi-eGFP-MSCs or their CM however, IL-6, IL-12p40, and TNF-a secretion was significant reduced.	This protective effect was associated with several anti inflammatory response mechanisms, including a reduction in peripheral T-cell proliferative responses, a decrease in pro inflammatory cytokine secretion as well as a preferential inhibition of Th17-mediated neuroinflammation.	23369732	Details
HLA-DQA1	Interferon beta-1a	N/A	N/A	N/A	Interaction between the genes from GWAS and drugs known for multiple sclerosis	N/A	35713861	Details
HLA-DQA1	Interferon beta-1b	N/A	N/A	N/A	Interaction between the genes from GWAS and drugs known for multiple sclerosis	N/A	35713861	Details
HLA-DQA1	Azathioprine	N/A	N/A	N/A	Interaction between the genes from GWAS and drugs known for multiple sclerosis	N/A	35713861	Details
CD58	Mitoxantrone	N/A	N/A	N/A	Interaction between the genes from GWAS and drugs known for multiple sclerosis	N/A	35713861	Details
CD58	Interferon beta-1a	N/A	N/A	N/A	Interaction between the genes from GWAS and drugs known for multiple sclerosis	N/A	35713861	Details
CD58	Interferon beta-1b	N/A	N/A	N/A	Interaction between the genes from GWAS and drugs known for multiple sclerosis	N/A	35713861	Details
HLA-DRB1	Azathioprine	N/A	N/A	N/A	Interaction between the genes from GWAS and drugs known for multiple sclerosis	N/A	35713861	Details
IL12A	Prednisone	N/A	N/A	N/A	Interaction between the genes from GWAS and drugs known for multiple sclerosis	N/A	35713861	Details
IL12A	Azathioprine	N/A	N/A	N/A	Interaction between the genes from GWAS and drugs known for multiple sclerosis	N/A	35713861	Details
STAT4	Methylprednisolone	N/A	N/A	N/A	Interaction between the genes from GWAS and drugs known for multiple sclerosis	N/A	35713861	Details
STAT4	Prednisolone	N/A	N/A	N/A	Interaction between the genes from GWAS and drugs known for multiple sclerosis	N/A	35713861	Details
Ag	Anti-TCR Antibody Treatment	inhibitor	EAE	B10.PL and PL/J mice	Administration of anti-TCR V6 mAb leads to protection from EAE	N/A	17475828	Details
Pdp2	ICER/CREM gene	inhibitor	EAE	C57BL/6J mice	suppresses the expression of PDP2.	PDP2 suppresses Th17 differentiation and Th17 cell-specific PDP2 inhibition accelerates EAE.	30150402	Details
Ifng	pVAXhsp65 Vaccination	inhibitor	EAE	Lewis rats	In addition, it downmodulated IFN-γ and IL-10 production by peripheral lymphoid organs.	This modulatory effect observed on cytokine production could explain the reduced inflammation.	20407280	Details
Il10	pVAXhsp65 Vaccination	inhibitor	EAE	Lewis rats	In addition, it downmodulated IFN-γ and IL-10 production by peripheral lymphoid organs.	This modulatory effect observed on cytokine production could explain the reduced inflammation.	20407280	Details
Il5	gene therapy with autoAg	activator	EAE	C57Bl/6J mice	In conclusion, this study demonstrates that a cell therapy using BMC expressing an autoAg can induce Ag-specific tolerance and ameliorate established EAE even in a nonmyeloablative setting.	Both IL-5 and IL-10 were reported to mediate Tr1 effects.	19277013	Details
Il10	gene therapy with autoAg	activator	EAE	C57Bl/6J mice	In conclusion, this study demonstrates that a cell therapy using BMC expressing an autoAg can induce Ag-specific tolerance and ameliorate established EAE even in a nonmyeloablative setting.	Both IL-5 and IL-10 were reported to mediate Tr1 effects.	19277013	Details
Bcl-2	670 nm light treatment	activator	EAE	C57Bl/6J mice	Animals receiving 670 nm light treatment also exhibited up-regulation of the Bcl-2 anti-apoptosis gene.	N/A	23840675	Details
Il7r	novel antisense oligonucleotides (ASOs)	inhibitor	EAE	N/A	Supporting their potential for therapeutic targeting, we showed that lead anti sIL7R ASOs correct the enhanced exon 6 exclusion imposed by the MS risk allele of rs6897932, whereas lead pro-sIL7R ASOs phenocopy it.	In this study, we identified novel antisense oligonucleotides (ASOs) that effectively control the inclusion (anti-sIL7R ASOs) or exclusion (pro-sIL7R ASOs) of this exon in a dose-dependent fashion.	35613883	Details
Il17a	E2 treatment	inhibitor	EAE	C57Bl/6J mice	Additionally, E2 treatment drastically reduced the production of interleukin-17 (IL-17) in the periphery of immunized mice.	N/A	19302141	Details
Il12b	siRNA-IL-23 treatment	inhibitor	EAE	rats	siRNA-IL-23 treatment downregulated IL-12, IL-17 and IL-23 mRNAs.	First, as shown in the present study, siRNA-IL-23 treatment suppressed the development of both Th1 and Th17 cells and related key cytokines.	22989513	Details
Il17	siRNA-IL-23 treatment	inhibitor	EAE	rats	siRNA-IL-23 treatment downregulated IL-12, IL-17 and IL-23 mRNAs.	First, as shown in the present study, siRNA-IL-23 treatment suppressed the development of both Th1 and Th17 cells and related key cytokines.	22989513	Details
Il23a	siRNA-IL-23 treatment	inhibitor	EAE	rats	siRNA-IL-23 treatment downregulated IL-12, IL-17 and IL-23 mRNAs.	First, as shown in the present study, siRNA-IL-23 treatment suppressed the development of both Th1 and Th17 cells and related key cytokines.	22989513	Details
Il1b	HSV-1-mediated IL-1 receptor antagonist gene therapy	inhibitor	EAE	C57Bl/6J mice	Proinflammatory cytokine mRNAs are downregulated in the brain from C57BL/6 EAE mice.	The decreased number of CNS-infiltrating macrophages can determine decreased levels of monocyte-related proinflammatory cytokine mRNA such as IL-1b, IL-6 and TNF-a.	16929354	Details
Il6	HSV-1-mediated IL-1 receptor antagonist gene therapy	inhibitor	EAE	C57Bl/6J mice	Proinflammatory cytokine mRNAs are downregulated in the brain from C57BL/6 EAE mice.	The decreased number of CNS-infiltrating macrophages can determine decreased levels of monocyte-related proinflammatory cytokine mRNA such as IL-1b, IL-6 and TNF-a.	16929354	Details
Tnf	HSV-1-mediated IL-1 receptor antagonist gene therapy	inhibitor	EAE	C57Bl/6J mice	Proinflammatory cytokine mRNAs are downregulated in the brain from C57BL/6 EAE mice.	The decreased number of CNS-infiltrating macrophages can determine decreased levels of monocyte-related proinflammatory cytokine mRNA such as IL-1b, IL-6 and TNF-a.	16929354	Details
Ifng	HSV-1-mediated IL-1 receptor antagonist gene therapy	inhibitor	EAE	C57Bl/6J mice	Proinflammatory cytokine mRNAs are downregulated in the brain from C57BL/6 EAE mice.	The decreased number of CNS-infiltrating macrophages can determine decreased levels of monocyte-related proinflammatory cytokine mRNA such as IL-1b, IL-6 and TNF-a.	16929354	Details
Mbp	anti-TGF-b treatment	inhibitor	EAE	Lewis rats	The anti-TGF-b treatment, however, has no effect on the defect of BN and BN-1L rats to generate a Th1 immune response as illustrated by the absence of IFN-g production upon in vitro restimulation with MBP and EAE peptide.	N/A	10331018	Details
Il23a	herpes simplex virus-based gene therapy	inhibitor	EAE	BALB/c mice	On the contrary, in the R8308 (IL-10 expression) treated mice, the expression of IL-23 was decreased.	however, a downregulating role for IL-10 in control of IL-23 expression.	15196670	Details
Il10	FOXP3-EXOs treatment	activator	EAE	C57BL/6 mice	Moreover, the FOXP3-EXOs treatment resulted in obvious increases in the levels of regulatory T (Treg) cells and IL-10, whereas levels of T helper 1 (Th1) cells, Th17 cells, IFN-γ, IL-6, and IL-17 decreased significantly in the splenocyte culture of EAE mice.	our findings that FOXP3-EXOs regulated Th/Treg immune homeostasis in vitro and in vivo.	35928722	Details
Ifng	FOXP3-EXOs treatment	inhibitor	EAE	C57BL/6 mice	Moreover, the FOXP3-EXOs treatment resulted in obvious increases in the levels of regulatory T (Treg) cells and IL-10, whereas levels of T helper 1 (Th1) cells, Th17 cells, IFN-γ, IL-6, and IL-17 decreased significantly in the splenocyte culture of EAE mice.	our findings that FOXP3-EXOs regulated Th/Treg immune homeostasis in vitro and in vivo.	35928722	Details
Il6	FOXP3-EXOs treatment	inhibitor	EAE	C57BL/6 mice	Moreover, the FOXP3-EXOs treatment resulted in obvious increases in the levels of regulatory T (Treg) cells and IL-10, whereas levels of T helper 1 (Th1) cells, Th17 cells, IFN-γ, IL-6, and IL-17 decreased significantly in the splenocyte culture of EAE mice.	our findings that FOXP3-EXOs regulated Th/Treg immune homeostasis in vitro and in vivo.	35928722	Details
Il17a	FOXP3-EXOs treatment	inhibitor	EAE	C57BL/6 mice	Moreover, the FOXP3-EXOs treatment resulted in obvious increases in the levels of regulatory T (Treg) cells and IL-10, whereas levels of T helper 1 (Th1) cells, Th17 cells, IFN-γ, IL-6, and IL-17 decreased significantly in the splenocyte culture of EAE mice.	our findings that FOXP3-EXOs regulated Th/Treg immune homeostasis in vitro and in vivo.	35928722	Details
Il2	treatment with the MHC variant peptide	activator	EAE	C57BL/6 mice	In contrast, MOG 35–55-specific T cells from me-v/β mice secrete significant amounts of IL-2 (1668 pg/ml) when stimulated with MOG Ag and also following treatment with the MHC variant peptide.	N/A	18981103	Details
Nedd8	specific inhibitor pevonedistat (MLN4924)	inhibitor	EAE	C57BL/6 mice	Finally, we demonstrated that inhibition of NEDD8 activating enzyme using the specific inhibitor pevonedistat (MLN4924) significantly ameliorated disease severity in murine experimental autoimmune encephalomyelitis.	N/A	33374005	Details
CD21	IFN-beta treatment	inhibitor	MS	N/A	On -IFN treatment serum sCD21 concentrations further decreased.	N/A	22137275	Details
Ccl2	IL-4 therapy(The ependymal route to cytokine-gene therapy)	inhibitor	EAE	AB/H mice	In the therapeutic protocol, the protection is owing to an in situ downregulation of expression of pro-inflammatory chemokines[e.g. monocyte chemoattractant protein 1 (MCP-1) and regulated on activation normal T-cell expressed and secreted (RANTES)] and cytokines (e.g. IL-1β and TNF-α).	In turn, downregulation of expression of these chemokines and cytokines deactivates macrophages already recruited within the CNS, possibly through the activation of resident microglia.	11525938	Details
Ccl5	IL-4 therapy(The ependymal route to cytokine-gene therapy)	inhibitor	EAE	AB/H mice	In the therapeutic protocol, the protection is owing to an in situ downregulation of expression of pro-inflammatory chemokines[e.g. monocyte chemoattractant protein 1 (MCP-1) and regulated on activation normal T-cell expressed and secreted (RANTES)] and cytokines (e.g. IL-1β and TNF-α).	In turn, downregulation of expression of these chemokines and cytokines deactivates macrophages already recruited within the CNS, possibly through the activation of resident microglia.	11525938	Details
Il1b	IL-4 therapy(The ependymal route to cytokine-gene therapy)	inhibitor	EAE	AB/H mice	In the therapeutic protocol, the protection is owing to an in situ downregulation of expression of pro-inflammatory chemokines[e.g. monocyte chemoattractant protein 1 (MCP-1) and regulated on activation normal T-cell expressed and secreted (RANTES)] and cytokines (e.g. IL-1β and TNF-α).	In turn, downregulation of expression of these chemokines and cytokines deactivates macrophages already recruited within the CNS, possibly through the activation of resident microglia.	11525938	Details
Tnf	IL-4 therapy(The ependymal route to cytokine-gene therapy)	inhibitor	EAE	AB/H mice	In the therapeutic protocol, the protection is owing to an in situ downregulation of expression of pro-inflammatory chemokines[e.g. monocyte chemoattractant protein 1 (MCP-1) and regulated on activation normal T-cell expressed and secreted (RANTES)] and cytokines (e.g. IL-1β and TNF-α).	In turn, downregulation of expression of these chemokines and cytokines deactivates macrophages already recruited within the CNS, possibly through the activation of resident microglia.	11525938	Details
Tnfrsf1a	IFN-β-treated	activator	EAE	C57BL/6 mice	During the recovery phase, the mRNA level of TNFR1 was also significantly increased in CNSinfiltrating cells from IFN-g treated mice compared with controls.	Our results further challenge the exclusive detrimental role of IFN-g in the CNS during EAE/multiple sclerosis, and indicate that CNS-confined inflammation may induce protective immunological countermechanisms leading to a faster clearance of encephalitogenic T cells by apoptosis, thus restoring the immune privilege of the CNS.	11466408	Details
IFNG	IFN-β-treated	inhibitor	MS	N/A	We propose that the therapeutic effect of IFN-β in multiple sclerosis may rest, at least in part, on its exquisite ability to induce high levels of PKR in the cell and thereby to limit IFN-γ mRNA translation through this negative feedback loop, blocking the excessive IFN-γ gene expression that precedes clinical attacks.	We propose that the therapeutic effect of IFN-β in multiple sclerosis may rest, at least in part, on its exquisite ability to induce high levels of PKR in the cell and thereby to limit IFN-γ mRNA translation through this negative feedback loop, blocking the excessive IFN-γ gene expression that precedes clinical attacks.	16474427	Details
Ifng	IFN-β-treated	inhibitor	EAE	C57BL/6 mice	Th1 and Th17 cells in IFN-β-treated mice were significantly reduced, and the levels of cytokines, such as IFN-γ, IL-17, and OPN, were significantly decreased in splenocyte supernatants as well as the levels of corresponding transcription factors.	IFN-β inhibited downstream inflammatory cytokines through the inhibition of PI3K/AKT/NF-κB axis and p38, JNK-MAPK, as well as the regulation of mTOR complexes.	29127843	Details
Il17a	IFN-β-treated	inhibitor	EAE	C57BL/6 mice	Th1 and Th17 cells in IFN-β-treated mice were significantly reduced, and the levels of cytokines, such as IFN-γ, IL-17, and OPN, were significantly decreased in splenocyte supernatants as well as the levels of corresponding transcription factors.	IFN-β inhibited downstream inflammatory cytokines through the inhibition of PI3K/AKT/NF-κB axis and p38, JNK-MAPK, as well as the regulation of mTOR complexes.	29127843	Details
Spp1	IFN-β-treated	inhibitor	EAE	C57BL/6 mice	Th1 and Th17 cells in IFN-β-treated mice were significantly reduced, and the levels of cytokines, such as IFN-γ, IL-17, and OPN, were significantly decreased in splenocyte supernatants as well as the levels of corresponding transcription factors.	IFN-β inhibited downstream inflammatory cytokines through the inhibition of PI3K/AKT/NF-κB axis and p38, JNK-MAPK, as well as the regulation of mTOR complexes.	29127843	Details
P38	IFN-β-treated	inhibitor	EAE	C57BL/6 mice	IFN-β inhibited downstream inflammatory cytokines through the inhibition of PI3K/AKT/NF-κB axis and p38, JNK-MAPK.	IFN-β inhibited downstream inflammatory cytokines through the inhibition of PI3K/AKT/NF-κB axis and p38, JNK-MAPK, as well as the regulation of mTOR complexes.	29127843	Details
Akt1	IFN-β-treated	inhibitor	EAE	C57BL/6 mice	IFN-β inhibited downstream inflammatory cytokines through the inhibition of PI3K/AKT/NF-κB axis and p38, JNK-MAPK.	IFN-β inhibited downstream inflammatory cytokines through the inhibition of PI3K/AKT/NF-κB axis and p38, JNK-MAPK, as well as the regulation of mTOR complexes.	29127843	Details
Nfkb1	IFN-β-treated	inhibitor	EAE	C57BL/6 mice	IFN-β inhibited downstream inflammatory cytokines through the inhibition of PI3K/AKT/NF-κB axis and p38, JNK-MAPK.	IFN-β inhibited downstream inflammatory cytokines through the inhibition of PI3K/AKT/NF-κB axis and p38, JNK-MAPK, as well as the regulation of mTOR complexes.	29127843	Details
Epha7	IFN-β-treated	inhibitor	EAE	C57BL/6 mice	IFN-β inhibited downstream inflammatory cytokines through the inhibition of PI3K/AKT/NF-κB axis and p38, JNK-MAPK.	IFN-β inhibited downstream inflammatory cytokines through the inhibition of PI3K/AKT/NF-κB axis and p38, JNK-MAPK, as well as the regulation of mTOR complexes.	29127843	Details
Mapk8	IFN-β-treated	inhibitor	EAE	C57BL/6 mice	IFN-β inhibited downstream inflammatory cytokines through the inhibition of PI3K/AKT/NF-κB axis and p38, JNK-MAPK.	IFN-β inhibited downstream inflammatory cytokines through the inhibition of PI3K/AKT/NF-κB axis and p38, JNK-MAPK, as well as the regulation of mTOR complexes.	29127843	Details
Trem2	T3 and Sob-AM2 treatment	activator	EAE	C57BL/6 mice	Treatment of EAE mice with T3 and Sob-AM2 upregulates TREM2 expression in diseased spinal cord regions	T3 and sobetirome suppress pro-inflammatory cytokine production from myeloid cells and induce phagocytic behavior in microglia, both of which are phenotypes that result from activation of the TREM2 pathway.	34375614	Details
Il6	curcumin-treated	inhibitor	EAE	C57BL/6 mice	Gene expression analyses revealed that treatment with curcumin could lead to a significant reduction in the expression levels of pro-inflammatory cytokine coding genes including IL-6, IL-17, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ as well as a significant increase in the expression level of transforming growth factor (TGF)-β (p = 0.006) as an anti-inflammatory cytokine.	curcumin prevents the nuclear factor kB-mediated transcription of inflammatory cytokines.	31033006	Details
Il17a	curcumin-treated	inhibitor	EAE	C57BL/6 mice	Gene expression analyses revealed that treatment with curcumin could lead to a significant reduction in the expression levels of pro-inflammatory cytokine coding genes including IL-6, IL-17, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ as well as a significant increase in the expression level of transforming growth factor (TGF)-β (p = 0.006) as an anti-inflammatory cytokine.	curcumin prevents the nuclear factor kB-mediated transcription of inflammatory cytokines.	31033006	Details
Tnf	curcumin-treated	inhibitor	EAE	C57BL/6 mice	Gene expression analyses revealed that treatment with curcumin could lead to a significant reduction in the expression levels of pro-inflammatory cytokine coding genes including IL-6, IL-17, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ as well as a significant increase in the expression level of transforming growth factor (TGF)-β (p = 0.006) as an anti-inflammatory cytokine.	curcumin prevents the nuclear factor kB-mediated transcription of inflammatory cytokines.	31033006	Details
Ifng	curcumin-treated	inhibitor	EAE	C57BL/6 mice	Gene expression analyses revealed that treatment with curcumin could lead to a significant reduction in the expression levels of pro-inflammatory cytokine coding genes including IL-6, IL-17, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ as well as a significant increase in the expression level of transforming growth factor (TGF)-β (p = 0.006) as an anti-inflammatory cytokine.	curcumin prevents the nuclear factor kB-mediated transcription of inflammatory cytokines.	31033006	Details
Tgfb1	curcumin-treated	activator	EAE	C57BL/6 mice	Gene expression analyses revealed that treatment with curcumin could lead to a significant reduction in the expression levels of pro-inflammatory cytokine coding genes including IL-6, IL-17, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ as well as a significant increase in the expression level of transforming growth factor (TGF)-β (p = 0.006) as an anti-inflammatory cytokine.	curcumin prevents the nuclear factor kB-mediated transcription of inflammatory cytokines.	31033006	Details
Gpx1	curcumin-treated	activator	EAE	C57BL/6 mice	Moreover, the expression of glutathione peroxidase (GPX)-1 gene and the activity of anti-oxidant enzymes were significantly higher in curcumin-treated mice.	N/A	31033006	Details
Il17a	CRAC channel blockers	inhibitor	EAE	C57BL/6 mice	In support of our in vitro and ex vivo data, we observed a predominant reduction in IL-17A+ population, whereas that of IFN-g+ cells was not significantly reduced.	Orai1 blockers had a potent anti-inflammatory effect in vivo.	24307733	Details
Rora	CRAC channel blockers	inhibitor	EAE	C57BL/6 mice	The mRNA levels of RORa and RORgt were dramatically reduced, whereas those of T-bet and Foxp3 were not significantly affected.	Orai1 blockers had a potent anti-inflammatory effect in vivo.	24307733	Details
Rorc	CRAC channel blockers	inhibitor	EAE	C57BL/6 mice	The mRNA levels of RORa and RORgt were dramatically reduced, whereas those of T-bet and Foxp3 were not significantly affected.	Orai1 blockers had a potent anti-inflammatory effect in vivo.	24307733	Details
Icam1	IGF-1/IGFBP3–treated	inhibitor	EAE	(PL 3 SJL)F1 mice	Possible mechanisms that could explain the altered disease in IGF-1/IGFBP3–treated mice included(a) IGF-1/IGFBP3 administration delayed the onset of EAE by downregulating ICAM-1 gene expression in the central nervous system.	The changes in ICAM-1 gene expression we observed may merely reflect differences in inflammatory cell infiltration, but also provide further evidence of a mechanism for retarded entry of inflammatory cells into the CNS in mice receiving IGF-1 or IGF-1/IGFBP3.	9541512	Details
Pdgfra	T3/NSCs treatment	activator	EAE	rat	Furthermore, T3/NSCs and GDNF-T3/NSCs grafting increased the expression of mRNA for PDGFR, GalC, and MBP in lesion areas of brain compared with NSCs grafting, and the expression of mRNA for GalC and MBP in GDNF-T3/NSCs group was higher than that in T3/NSCs group.	The results suggest that T3/NSCs, especially GDNF-T3/NSCs, more effectively reduce CNS-infiltrating inflammatory cells, thus exerting better effect than NSCs on EAE.	26881104	Details
Galc	T3/NSCs treatment	activator	EAE	rat	Furthermore, T3/NSCs and GDNF-T3/NSCs grafting increased the expression of mRNA for PDGFR, GalC, and MBP in lesion areas of brain compared with NSCs grafting, and the expression of mRNA for GalC and MBP in GDNF-T3/NSCs group was higher than that in T3/NSCs group.	The results suggest that T3/NSCs, especially GDNF-T3/NSCs, more effectively reduce CNS-infiltrating inflammatory cells, thus exerting better effect than NSCs on EAE.	26881104	Details
Mbp	T3/NSCs treatment	activator	EAE	rat	Furthermore, T3/NSCs and GDNF-T3/NSCs grafting increased the expression of mRNA for PDGFR, GalC, and MBP in lesion areas of brain compared with NSCs grafting, and the expression of mRNA for GalC and MBP in GDNF-T3/NSCs group was higher than that in T3/NSCs group.	The results suggest that T3/NSCs, especially GDNF-T3/NSCs, more effectively reduce CNS-infiltrating inflammatory cells, thus exerting better effect than NSCs on EAE.	26881104	Details
Pdgfra	GDNF-T3/NSCs treatment	activator	EAE	rat	Furthermore, T3/NSCs and GDNF-T3/NSCs grafting increased the expression of mRNA for PDGFR, GalC, and MBP in lesion areas of brain compared with NSCs grafting, and the expression of mRNA for GalC and MBP in GDNF-T3/NSCs group was higher than that in T3/NSCs group.	The results suggest that T3/NSCs, especially GDNF-T3/NSCs, more effectively reduce CNS-infiltrating inflammatory cells, thus exerting better effect than NSCs on EAE.	26881104	Details
Galc	GDNF-T3/NSCs treatment	activator	EAE	rat	Furthermore, T3/NSCs and GDNF-T3/NSCs grafting increased the expression of mRNA for PDGFR, GalC, and MBP in lesion areas of brain compared with NSCs grafting, and the expression of mRNA for GalC and MBP in GDNF-T3/NSCs group was higher than that in T3/NSCs group.	The results suggest that T3/NSCs, especially GDNF-T3/NSCs, more effectively reduce CNS-infiltrating inflammatory cells, thus exerting better effect than NSCs on EAE.	26881104	Details
Mbp	GDNF-T3/NSCs treatment	activator	EAE	rat	Furthermore, T3/NSCs and GDNF-T3/NSCs grafting increased the expression of mRNA for PDGFR, GalC, and MBP in lesion areas of brain compared with NSCs grafting, and the expression of mRNA for GalC and MBP in GDNF-T3/NSCs group was higher than that in T3/NSCs group.	The results suggest that T3/NSCs, especially GDNF-T3/NSCs, more effectively reduce CNS-infiltrating inflammatory cells, thus exerting better effect than NSCs on EAE.	26881104	Details
Tnf	fingolimod-treated	inhibitor	EAE	C57BL/6	Pretreatment of bone marrow-derived DCs with fingolimod resulted in significantly less TNFα, IFN-γ and IL-10 production by 2D2 T cells.	In this study, we found that fingolimod treatment reduced the ability of MOG35–55-loaded murine DCs to prime antigen specifically naive 2D2 T cells into pro-inflammatory Th1 cells.	25732840	Details
Ifng	fingolimod-treated	inhibitor	EAE	C57BL/6	Pretreatment of bone marrow-derived DCs with fingolimod resulted in significantly less TNFα, IFN-γ and IL-10 production by 2D2 T cells.	In this study, we found that fingolimod treatment reduced the ability of MOG35–55-loaded murine DCs to prime antigen specifically naive 2D2 T cells into pro-inflammatory Th1 cells.	25732840	Details
Il10	fingolimod-treated	inhibitor	EAE	C57BL/6	Pretreatment of bone marrow-derived DCs with fingolimod resulted in significantly less TNFα, IFN-γ and IL-10 production by 2D2 T cells.	In this study, we found that fingolimod treatment reduced the ability of MOG35–55-loaded murine DCs to prime antigen specifically naive 2D2 T cells into pro-inflammatory Th1 cells.	25732840	Details
Mog	IL-1b treatment	inhibitor	EAE	SJL/J mice	Interestingly, both IL-1h and TNF-a markedly inhibited the expression of MOG, CNPase, and PLP but not MBP.	Taken together, these studies suggest that proinflammatory cytokines inhibit the expression of myelin genes in human primary oligodendrocytes through the alteration of cellular redox.	16109311	Details
Cnp	IL-1b treatment	inhibitor	EAE	SJL/J mice	Interestingly, both IL-1h and TNF-a markedly inhibited the expression of MOG, CNPase, and PLP but not MBP.	Taken together, these studies suggest that proinflammatory cytokines inhibit the expression of myelin genes in human primary oligodendrocytes through the alteration of cellular redox.	16109311	Details
Plp1	IL-1b treatment	inhibitor	EAE	SJL/J mice	Interestingly, both IL-1h and TNF-a markedly inhibited the expression of MOG, CNPase, and PLP but not MBP.	Taken together, these studies suggest that proinflammatory cytokines inhibit the expression of myelin genes in human primary oligodendrocytes through the alteration of cellular redox.	16109311	Details
Mog	TNF-a treatment	inhibitor	EAE	SJL/J mice	Interestingly, both IL-1h and TNF-a markedly inhibited the expression of MOG, CNPase, and PLP but not MBP.	Taken together, these studies suggest that proinflammatory cytokines inhibit the expression of myelin genes in human primary oligodendrocytes through the alteration of cellular redox.	16109311	Details
Cnp	TNF-a treatment	inhibitor	EAE	SJL/J mice	Interestingly, both IL-1h and TNF-a markedly inhibited the expression of MOG, CNPase, and PLP but not MBP.	Taken together, these studies suggest that proinflammatory cytokines inhibit the expression of myelin genes in human primary oligodendrocytes through the alteration of cellular redox.	16109311	Details
Plp1	TNF-a treatment	inhibitor	EAE	SJL/J mice	Interestingly, both IL-1h and TNF-a markedly inhibited the expression of MOG, CNPase, and PLP but not MBP.	Taken together, these studies suggest that proinflammatory cytokines inhibit the expression of myelin genes in human primary oligodendrocytes through the alteration of cellular redox.	16109311	Details
KLRB1	(IFN)-b treatment	inhibitor	MS	Scandinavian	KLRB1 expression decreased significantly (Po0.001) after interferon (IFN)-b treatment.	KLRB1 was expressed in T and NK cells, and expression mainly decreased in NK cells in patients treated with IFN-b.	21610746	Details
Bax	treatment with curcumin	inhibitor	EAE	C57BL/6 mice	After treatment with curcumin, the expression of Bcl-2 was decreased and that of Bax and active caspase-3 was increased.	The Bcl-2 protein family plays an important role in the induction and control of apoptosis. Bcl2 (an anti-apoptotic protein) and Bax (a pro-apoptotic protein) are the two important members14.	31696502	Details
Bcl2	treatment with curcumin	activator	EAE	C57BL/6 mice	After treatment with curcumin, the expression of Bcl-2 was decreased and that of Bax and active caspase-3 was increased.	The Bcl-2 protein family plays an important role in the induction and control of apoptosis. Bcl2 (an anti-apoptotic protein) and Bax (a pro-apoptotic protein) are the two important members14.	31696502	Details
Tnf	treatment with the KCNN4 blocker	inhibitor	EAE	C57BL/6 mice	Treatment with TRAM-34 reduced the level of proinflammatory cytokines IFN-γ and TNF-a.	A selective KCNN4 ion-channel blocker, TRAM-34, protected mice from developing EAE, a T cell mediated inflammatory disease, primarily by reducing the level of IFN-γ and TNF-a proteins in the cell infiltrated areas of the central nervous system.	15770697	Details
Ifng	treatment with the KCNN4 blocker	inhibitor	EAE	C57BL/6 mice	Treatment with TRAM-34 reduced the level of proinflammatory cytokines IFN-γ and TNF-a.	A selective KCNN4 ion-channel blocker, TRAM-34, protected mice from developing EAE, a T cell mediated inflammatory disease, primarily by reducing the level of IFN-γ and TNF-a proteins in the cell infiltrated areas of the central nervous system.	15770697	Details
Ifng	IS IL-4 DNA	inhibitor	EAE	Lewis rats	The MBP-specific expression of IFN-γ from stimulated splenocytes was considerably decreased by the IS IL-4 DNA transfer group both in the preventive and therapeutic experiments while IM transfer had this effect only in the preventive protocol.	Spinal cord inflammation was considerably reduced in the IS IL-4 DNA transfer group.	16564024	Details
Bax	G-CSF treatment	activator	EAE	C57BL/6 mice	Moreover, G-CSF promoted the G0/G1 to S phase transition of MOG35-55 autoreactive T cells inducing apoptosis and elevating Bax gene expression of apoptosis marker.	Bax activation leads to mitochondrial dysfunction and cell death. Bax protein forms heterodimers with the apoptosis inhibitor Bcl-2, and the relative levels of these two molecules determine the cell's death.	27771353	Details
Ifng	G-CSF treatment	inhibitor	EAE	C57BL/6 mice	G-CSF therapy reduced pro-inflammatory cytokine IL-1a, TNF-b and NO levels in brain tissue, whereas the anti-inflammatory cytokine IL-4 content was increased.	N/A	27771353	Details
Il1b	G-CSF treatment	inhibitor	EAE	C57BL/6 mice	G-CSF therapy reduced pro-inflammatory cytokine IL-1a, TNF-b and NO levels in brain tissue, whereas the anti-inflammatory cytokine IL-4 content was increased.	N/A	27771353	Details
Il17a	G-CSF treatment	inhibitor	EAE	C57BL/6 mice	G-CSF therapy reduced pro-inflammatory cytokine IL-1a, TNF-b and NO levels in brain tissue, whereas the anti-inflammatory cytokine IL-4 content was increased.	N/A	27771353	Details
Il2	G-CSF treatment	inhibitor	EAE	C57BL/6 mice	G-CSF therapy reduced pro-inflammatory cytokine IL-1a, TNF-b and NO levels in brain tissue, whereas the anti-inflammatory cytokine IL-4 content was increased.	N/A	27771353	Details
Tnf	G-CSF treatment	inhibitor	EAE	C57BL/6 mice	G-CSF therapy reduced pro-inflammatory cytokine IL-1a, TNF-b and NO levels in brain tissue, whereas the anti-inflammatory cytokine IL-4 content was increased.	N/A	27771353	Details
Il4	G-CSF treatment	activator	EAE	C57BL/6 mice	G-CSF therapy reduced pro-inflammatory cytokine IL-1a, TNF-b and NO levels in brain tissue, whereas the anti-inflammatory cytokine IL-4 content was increased.	Increase IL-4 and IL-10 secretions, elevate a CD4+CD25+ T cell subset that inhibits inflammatory infiltration and demyelination within the CNS of EAE.	27771353	Details
Il10	G-CSF treatment	activator	EAE	C57BL/6 mice	G-CSF therapy reduced pro-inflammatory cytokine IL-1a, TNF-b and NO levels in brain tissue, whereas the anti-inflammatory cytokine IL-4 content was increased.	Increase IL-4 and IL-10 secretions, elevate a CD4+CD25+ T cell subset that inhibits inflammatory infiltration and demyelination within the CNS of EAE.	27771353	Details
PDCD1	alemtuzumab treatment	activator	MS	RRMS patients	CD4 expression of the inhibitory receptors [programmed death-1 (PD-1) and lymphocyte activation gene-3 (LAG-3)] was increased 6–9 mo after alemtuzumab.	CD4 expansion may also be limited by upregulation of the inhibitory receptors PD-1 and LAG-3 and prolonged CD95 (Fas) expression.	24282306	Details
LAG3	alemtuzumab treatment	activator	MS	RRMS patients	CD4 expression of the inhibitory receptors [programmed death-1 (PD-1) and lymphocyte activation gene-3 (LAG-3)] was increased 6–9 mo after alemtuzumab.	CD4 expansion may also be limited by upregulation of the inhibitory receptors PD-1 and LAG-3 and prolonged CD95 (Fas) expression.	24282306	Details
Vcam1	Sativex	inhibitor	EAE	SJL/J mice	Sativex also reduced the expression of VCAM-1 and ICAM-1.	Sativex may restrict the permissiveness of immune cell infiltration into the CNS parenchyma.	25857324	Details
Icam1	Sativex	inhibitor	EAE	SJL/J mice	Sativex also reduced the expression of VCAM-1 and ICAM-1.	Sativex may restrict the permissiveness of immune cell infiltration into the CNS parenchyma.	25857324	Details
Il1b	Sativex	inhibitor	EAE	SJL/J mice	Sativex decreased microglial activity, down-regulated the expression of proinflammatory cytokines and up-regulated arginase-1 (Arg-1) and IL-10 in the spinal cord of TMEV-infected mice	Sativex could act as an immunomodulator, not only limiting the inflammation in TMEV-IDD mice but also promoting an anti-inflammatory environment.	25857324	Details
Tnf	Sativex	inhibitor	EAE	SJL/J mice	Sativex decreased microglial activity, down-regulated the expression of proinflammatory cytokines and up-regulated arginase-1 (Arg-1) and IL-10 in the spinal cord of TMEV-infected mice	Sativex could act as an immunomodulator, not only limiting the inflammation in TMEV-IDD mice but also promoting an anti-inflammatory environment.	25857324	Details
Ifng	Sativex	inhibitor	EAE	SJL/J mice	Sativex decreased microglial activity, down-regulated the expression of proinflammatory cytokines and up-regulated arginase-1 (Arg-1) and IL-10 in the spinal cord of TMEV-infected mice	Sativex could act as an immunomodulator, not only limiting the inflammation in TMEV-IDD mice but also promoting an anti-inflammatory environment.	25857324	Details
Arg1	Sativex	activator	EAE	SJL/J mice	Sativex decreased microglial activity, down-regulated the expression of proinflammatory cytokines and up-regulated arginase-1 (Arg-1) and IL-10 in the spinal cord of TMEV-infected mice	Sativex could act as an immunomodulator, not only limiting the inflammation in TMEV-IDD mice but also promoting an anti-inflammatory environment.	25857324	Details
Il10	Sativex	activator	EAE	SJL/J mice	Sativex decreased microglial activity, down-regulated the expression of proinflammatory cytokines and up-regulated arginase-1 (Arg-1) and IL-10 in the spinal cord of TMEV-infected mice	Sativex could act as an immunomodulator, not only limiting the inflammation in TMEV-IDD mice but also promoting an anti-inflammatory environment.	25857324	Details
Il17a	ADMSC-SPK1 treatment	inhibitor	EAE	mice	The expression level of IL-17A in mouse brain and spinal cord tissues was significantly reduced in the ADMSC group( t=10.323, P=0.013; t=7.422, P=0.008),and it was significantly lower in the ADMSC-SPK1 group than in the ADMSC group ( t=14.244, P=0.017; t=16.865, P=0.006).	The mechanism may be that ADMSC-SPK1 can markedly reduce the Th17/Treg cell ratio and decrease the release of related inflammatory cytokines in EAE mice.	33423722	Details
Foxp3	ADMSC-SPK3 treatment	activator	EAE	mice	The expression level of Foxp3 in the ADMSC group was significantly increased( t=14.544, P=0.008; t=9.420, P=0.002),and it was significantly higher in the ADMSC-SPK1 group than ADMSC group.	The mechanism may be that ADMSC-SPK1 can markedly reduce the Th17/Treg cell ratio and decrease the release of related inflammatory cytokines in EAE mice.	33423722	Details
myelin genes	Gemfibrozil	activator	experimental autoimmune encephalomyelitis	PPAR-α(-/-) and PPAR-β(-/-) mice	Furthermore, gemfibrozil treatment also led to the recruit ment of PPAR- to the PLP promoter in vivo in the spinal cord of experimental autoimmune encephalomyelitis mice and suppres sion of experimental autoimmune encephalomyelitis symptoms in PLP-T cell receptor transgenic mice.	Gemfibrozil, an FDA-approved drug for hyperlipidemia, stimulates the expression of myelin genes in primary human oligodendroglia via PPAR-β.	22879602	Details
Il10	IL-10 therapy	activator	MOG-EAE	Dark Agouti rats	This therapy is shown here to reverse inflammation induced paralysis, to reduce disease associated reduction in sensitivity to touch, to prevent the onset of allodynia, to reverse disease associated loss of body weight, and to suppress CNS glial activation associated with disease progression in this model.	The mechanisms by which IL-10 reduces glial activation include both transcriptional and translational actions including suppression of pro-inflammatory gene expression, upregulation of inflammatory cytokine decoy receptors, and reduction in the activation of transcription factors responsible for pro inflammatory gene activation.	18835435	Details
Adora1	Caffeine treatment	activator	EAE	mice (A1AR+/+) and mice (A1AR-/-)	Caffeine treatment augmented A1AR expression on microglia, with ensuing reduction of EAE severity, which was further enhanced by concomitant treatment with the A1AR agonist,adenosine amine congener.	However, A1AR acti vation after its upregulation by caffeine enhances related down stream signaling pathways,suppressing proinflammatory and augmenting anti-inflammatory responses, which diminish oligo dendrocyte cytotoxicity together with maintaining the integrity of the myelin sheath and associated axon.	14960625	Details
Pparg	PPARγ agonists	activator	EAE	C57BL/6 mice	Clinical symptoms were reduced by two other PPAR agonists,suggesting a role for PPAR activation in protective effects.	Ligands of the peroxisome proliferator-activated recep tor (PPAR) exert anti-inflammatory effects on glial cells,reduce proliferation and activation of T cells, and induce myelin gene expression.	12112074	Details
Ccl2	Allogeneic Mesenchymal Stem Cells	activator	EAE	C57BL/6 mice	In conclu sion, allogeneic MSCs can suppress the manifestations of EAE, yet retain the potential for alloimmunization.	Administration of allogeneic Balb/c-derived MSCs to C57Bl/6 mice with pre-established EAE led to a significant decrease in dis ease score over time comparable to that achieved with syngeneic MSCs, and was correlated with a significant blunting of immune cell infiltration to the spinal cord and reduced circulating levels of interferon-γ (IFN-γ) and interleukin-17.	19602999	Details
Stat3	FTY720 treatment	activator	EAE	S1PR1(S5A) mice (C57BL/6J background)	FTY720 treatment downregulated Th17 cell development via targeting STAT3 activation.	Long-term treatment with FTY720 induced significant lymphopenia and suppressed Th17 response in the peripheral immune system via downregulating STAT3 phosphorylation in both WT and S1PR1(S5A) mice.	27699272	Details
IL-10	NT-3-NSCs and NT-3/IL-10-NSCs treatment	inhibitor	EAE	C57BL/6 mice	These results indicate that IL-10 in the cocktail plays an important role in the inhibition of CNS inflammatory infiltration.	IL-10, an effective immunoregulatory cytokine.	27203442	Details
IL-17	NT-3/IL-10-NSCs and cocktail-NSCs	inhibitor	EAE	C57BL/6 mice	Overall, cocktail NSCs inhibited IFN-γ, IL-17, and GM-CSF production.	N/A	27203442	Details
Csf2	cocktail-NSCs	inhibitor	EAE	C57BL/6 mice	Overall, cocktail NSCs inhibited IFN-γ, IL-17, and GM-CSF production.	N/A	27203442	Details
Ifng	cocktail-NSCs	inhibitor	EAE	C57BL/6 mice	Overall, cocktail NSCs inhibited IFN-γ, IL-17, and GM-CSF production.	N/A	27203442	Details
Jag1	Jagged1 treatment	activator	MS	C57B6 mice	In vitro treatment with a Jagged1 agonist peptide modulated the T-cell activation network in PBMCs from patients with MS.	Our results suggested that the Jagged1-Notch pathway modulates Th1 function.	18030350	Details
Cdk5	N/A	inhibitor	EAE	C57BL/6 or B6D21 mice	These data define a distinct role for Cdk5 in lymphocyte biology and suggest that inhibition of this kinase may be beneficial in the treatment of T cell–mediated inflammatory disorders.	T cell receptor (TCR) stimulation leads to a rapid induction of Cdk5–p35 expression that is required for T lymphocyte activation.	20937706	Details
Ifng	GL3-treatment	inhibitor	EAE	SJL/J mice	Studies of type II NOS also demonstrated a significant reduction in both mRNA and protein expression at the height of disease in GL3-treated animals.	These results suggest that gd T cells contribute to the pathogenesis of EAE by regulating the influx of inflammatory cells into the spinal cord and by augmenting the proinflammatory cytokine profile of the inflammatory infiltrates.	9637509	Details
Il1	GL3-treatment	inhibitor	EAE	SJL/J mice	ELISA data confirmed the reduced levels of IL-1 and IL-6 at disease onset in GL3-treated animals, and pathologic analysis demonstrated a marked reduction in meningeal infiltrates at the same time point.	we showed previously that depletion of γδT cells using the mAb GL3 immediately before disease onset, or during the chronic phase, significantly ameliorated clinical severity.	9637509	Details
Il6	GL3-treatment	inhibitor	EAE	SJL/J mice	ELISA data confirmed the reduced levels of IL-1 and IL-6 at disease onset in GL3-treated animals, and pathologic analysis demonstrated a marked reduction in meningeal infiltrates at the same time point.	we showed previously that depletion of γδT cells using the mAb GL3 immediately before disease onset, or during the chronic phase, significantly ameliorated clinical severity.	9637509	Details
Tsc22d3	HGF therapy	activator	EAE	C57BL/6J (H-2b) female mice	In this study,we demonstrate that systemic HGF treatment ameliorates EAE through the development of tolerogenic dendritic cells (DCs) with high expression levels of glucocorticoid-induced leucine zipper (GILZ), a transcriptional repressor of gene expression and a key endogenous regulator of the inflammatory response.	Altogether, these results show that by inducing GILZ in DCs, HGF reproduces the mechanism of immune regulation induced by potent immunomodulatory factors such as IL-10, TGF-b1, and glucocorticoids and therefore that HGF therapy may have potential in the treatment of autoimmune dysfunctions.	25114100	Details
Ercc8	CsA treatment	inhibitor	EAE	C57BL/6 mice	During a follow-up period of 20 days, the observed clinical benefit could be attributed solely to CsA treatment.	In order to avoid acute or chronic rejection of cellular transplant in the CNS, as previously demonstrated by us and others.	21092405	Details
Kcna3	ADWX-1	inhibitor	EAE	Sprague-Dawley (SD) rats	ADWX-1 selectively inhibits TEM activation through regulating both Kv1.3 activity and expression	ADWX-1 ameliorates EAE with a cell selectivity mechanism	22761436	Details
inflammatory genes	FTY720 treatment	inhibitor	EAE	Dark Agouti (DA) rats	FTY720 downregulated inflammatory genes in addition to vascular adhesion molecules.	resulting in a proteolytic balance that favors preservation of blood-brain-barrier (BBB) integrity.	18540945	Details
Mmp9	FTY720 treatment	inhibitor	EAE	Dark Agouti (DA) rats	It decreased the matrix metalloproteinase gene MMP-9 and increased its counterregulator—tissue inhibitor of metalloproteinase, TIMP 1—resulting in a proteolytic balance that favors preservation of blood-brain-barrier(BBB)integrity.	resulting in a proteolytic balance that favors preservation of blood-brain-barrier (BBB) integrity.	18540945	Details
Timp1	FTY720 treatment	activator	EAE	Dark Agouti (DA) rats	It decreased the matrix metalloproteinase gene MMP-9 and increased its counterregulator—tissue inhibitor of metalloproteinase, TIMP 1—resulting in a proteolytic balance that favors preservation of blood-brain-barrier(BBB)integrity.	resulting in a proteolytic balance that favors preservation of blood-brain-barrier (BBB) integrity.	18540945	Details
Lif	LIFNano-CD4	activator	progressive course of EAE, and a relapsing, remitting disease course	C57BL / 6 mice	The efficacy and speed of LIFNano-CD4 in partially reversing paralysis starting as early as 4 days was unexpected.A significant dose-dependent effect on rate of recovery from the induced relapse that was dependent on the LIF cargo increased the recovery rate which is a hallmark of neuro-protection.In marked contrast, in those mice receiving LIFNano-CD4, plasma GM-CSF was significantly reduced.	LIF switches CD4 cells away from myelin-directed TH17 toward Treg, able to support myelin repair and neuro-protection given that Treg releases endogenous LIF.	35047909	Details
Il23r	AAV8 encoding the soluble sequence of IL-23R	inhibitor	EAE	N/A	Animals treated with AAV8/sIL23R showed a significant clinical improvement compared to mice treated with the null vector.This improvement was maintained stably until the end of the experiment. Subsequent immunological analysis in sIL23R treated animals showed a significant decrease in Interferon gamma (IFNγ) levels accompanied by an increase in the production of granulocyte macrophage colony-stimulating factor.	During MS neuropathology, antigen stimulated dendritic cells begin to secrete lymphocyte activator signals such as IL-23.IL-23, an interleukin member of the IL-12 family interacts with its membrane receptor to activate JAK kinases (JAK2 and TYK2) and then signal transducer and activator of transcription (STAT)3 and STAT4, whose action together with retinoid-related orphan receptor gamma t (RORγt) transcription factor leads to the differentiation and activation of the Th17 pathway. Therefore, IL-23, as a molecule involved in the stabilization and amplification of the Th17 phenotype and induction of the inflammatory response, is considered an interesting therapeutic target to treat MS.	29171419	Details
S1PR1	Fingolimod	activator	MS	Portugal	No significant differences for other lipids and lipid ratios were found in patient’s post-treatment compared with pre-treatment levels.Regarding apolipoproteins, a significant increase in ApoE was found at 12 months of treatment.At 6 months, patients had higher PPARγ mRNA expression in comparison to the baseline.Higher CD36 gene expression was also observed at 6 months in comparison to baseline .	Fingolimod was the first oral disease-modifying treatment (DMT) approved in MS. Fingolimod is a synthetic sphingosine analogue which once phosphorylated to sphingosine-1-phosphate (S1P) binds to several S1P receptors (S1PR).By inducing internalization and degradation of S1PR1, phospho-FTY720 impairs this egress, resulting in a significant reduction of circulating T and B cells and infiltration in the CNS.Within circulation, S1P is mainly present in high-density lipoprotein (HDL-C), and mediates the regulatory properties of this lipoprotein in immune responses.PPARs are ligand-activated transcriptional factors involved in the regulation of lipid and glucose metabolism and adaptive and innate immunity.PPAR can regulate gene expression also by interfering with other transcriptional factors and other proteins implicated in human disease. Cluster of Differentiation 36 (CD36) is a membrane receptor upregulated by PPARγ expressed in many cells that modulates immune functions and implicated in reparative mechanisms of MS lesions.	36590913	Details
MBTPS1	Fingolimod	inhibitor	MS	N/A	In this study, fingolimod significantly reduced the mean ARR in 47.2 and 88.6% at 1 and 2 years, respectively, and the percentage of relapse-free patients was ~75% at the end of the study without differences between the subgroups.In lymphocyte populations, no significant differences between HC and patients were observed before treatment, except for the percentage of LB1 cells composed mostly of CD11b+ cells, which was smaller in patients.We could verify that fingolimod affected practically all lymphocyte populations and subpopulations of B, T, and NK cells.As expected, a reduction of the percentages of CD3+, CD4+, CD20+, CD19+, TCM and TN, memory B (switched and no-switched), regulatory B, NK bright, and cytokine-producing cells (IFN, IL-17, and IL-2) was observed after treatment, with a relative increase in effector memory T (TEM), terminally differentiated effector T (TEMRA), NK, NK dim, NKT, Tregs, nave B, immature B, transitional B, CD5+ B, LB1, and plasmablast cells.Patients who achieved NEDA-3 and NEDA-4 status at 1 year had a significantly higher percentage of NK bright and plasmablast cells and a lower proportion of NK dim and IL-2-producing cells at baseline than NR patients.These patients were significantly more resistant to decreases in percentages of NK bright and LB1 cells and showed a greater decline of CD8 nave T and CD8+ CCR4+ CCR6+ cells than NR patients after 6 months of treatment.Fingolimod exerts powerful transcriptional effects on PBMCs of MS patients.A total of 16,818 filtered probes were used for the differential analyses, resulting in the identification of 3,805 upregulated and 3,741 downregulated genes in response to fingolimod.	Such therapies as fingolimod (Gilenya), a functional sphingosine-1-phosphate (S1P) antagonist, have been developed to retain the autoreactive lymphocytes within the lymph nodes. The phosphorylated form of fingolimod binds to four of five S1P-receptors (S1P1 and S1P3–5), resulting in aberrant internalization and degradation of the receptor on the cell surface and blockade of the egress and recirculation of activated CCR7+ and CD62+ lymphocytes from lymph nodes, such as central memory (TCM) and nave T (TN) cells.In addition, S1P receptors are differentially expressed in several tissues and have significant roles in a variety of cellular responses, including survival, inhibition of apoptosis, cardioprotection, activation of innate and adaptive immune systems, Treg differentiation, and promoting Th1 and Th17 differentiation in vitro and in vivo.	30090102	Details
Il13	IL-13 immune gene therapy (pCHMWS-IL-13-IRES-Pac LV plasmid)	activator	MS	C57BL/6J mice	We provide evidence that IL-13 directs the polarization of both brain-resident microglia and infiltrating macrophages towards an alternatively activated phenotype, thereby promoting the conversion of a pro-inflammatory environment toward an anti-inflammatory environment.IL-13 immune gene therapy is also able to limit lesion severity in a pre-existing inflammatory environment.	lentiviral vector-mediated expression of the immune-modulating cytokine interleukin 13 (IL-13) induces an alternative activation program in both microglia and macrophages conferring protection against severe oligodendrocyte loss and demyelination in the cuprizone mouse model for multiple sclerosis (MS).	27685637	Details
Csf1r	PLX3397	inhibitor	PMS	C57BL/6 N mice	Treatment with PLX3397 reduces the number of microglia and attenuates T-cell recruitment in the CNS of PLPmut mice and ameliorates neural damage in PLPmut mice.This leads to an amelioration of demyelination, axonopathic features and neuron loss in the retinotectal system, also reflected by reduced thinning of the inner retinal composite layer in longitudinal studies using noninvasive optical coherence tomography.	PLX3397, a potent inhibitor of the CSF-1R and targeting innate immune cells, attenuates neuroinflammation in our models by reducing numbers of resident microglia and attenuating T-lymphocyte recruitment in the CNS.	30565754	Details
Hdac2	combining valproic acid (VPA) with thyroid hormone (T3/T4)	inhibitor	EAE	Inbred DA/Kini rats	Treatment with VPA, T3 and VPA/T3 affects encephalitogenic CD4 + T cells in vitro. Treatment of encephalitogenic CD4 + T cells with VPA, T3, and VPA/T3 prior to transfer into nave rats reduces clinical signs of EAE. Acute treatment with VPA and T4 ameliorates clinical signs of EAE in DA rats. Treatment of EAE with VPA and T4 modulates the immune response,reduces numbers of Th1 cells in the brain and less fraction of Th1 cells infiltrating the brain and modulates the immune response and modulates immune response in peripheral tissues,prevents inflammatory demyelination in the brain.	HDAC inhibition can modulate encephalitogenic CD4 + T cells.One of the mechanisms by which treatment with VPA and the T3 precursor might be acting in the brain is by promoting oligodendrocyte lineage progression. Our data indicate that an acute treatment with VPA and T4 after the onset of EAE can produce persistent clinically relevant therapeutic effects by limiting the pathogenic immune reactions while promoting myelin gene expression.	25149263	Details
Ndufa6	complex I subunit gene therapy with NDUFA6(scAAV6-NDUFA2Flag)	activator	EAE	DBA/1J mice	Overexpression of NDUFA6Flag rescues the EAE-mediated visual dysfunction , EAE-mediated RGC loss , RNFL thinning , EAE axonal degeneration,RGC apoptosis and rescues EAE-mediated complex I dysfunction.NDUFA6 gene therapy provided long-term suppression of neurodegeneration in the EAE animal model suggesting that it may also ameliorate the mitochondrial dysfunction associated with permanent disability in optic neuritis and MS patients.	Mitochondrial dysfunction is recognized as one of the major contributing factors associated with neuronal and axonal loss in MS.It is a major target for damage induced by oxidative stress. Overall, it is believed that mitochondrial NDUFA6 is a crucial member in normal functioning of mitochondrial complex I and any alterations to this subunit adversely impacts respiratory chain function and ultimately cell viability.	25613946	Details
Shh	Niaspan	activator	EAE	SJL/J mice	Compared to the controls, neurological functional recovery was significantly increased in the Niaspan treated mice and inflammatory infiltrates were significantly reduced , HDL level, intact myelin area, newly formed oligodendrocytes, regenerating axons,gene and protein levels of sonic hedgehog (Shh)/Gli1 were significantly increased in the Niaspan treated mice .	Niaspan treatment improved functional recovery after EAE, possibly, via reducing inflammatory infiltrates and demyelination areas, and stimulating oligodendrogenesis and axonal regeneration. Niaspan mediated activation of Shh/Gli1 pathway may promote functional recovery post EAE.	18778774	Details
Gli1	Niaspan	activator	EAE	SJL/J mice	Compared to the controls, neurological functional recovery was significantly increased in the Niaspan treated mice and inflammatory infiltrates were significantly reduced , HDL level, intact myelin area, newly formed oligodendrocytes, regenerating axons,gene and protein levels of sonic hedgehog (Shh)/Gli1 were significantly increased in the Niaspan treated mice .	Niaspan treatment improved functional recovery after EAE, possibly, via reducing inflammatory infiltrates and demyelination areas, and stimulating oligodendrogenesis and axonal regeneration. Niaspan mediated activation of Shh/Gli1 pathway may promote functional recovery post EAE.	18778774	Details
Mog	MOG-Ig gene therapy(retrovirally transduced B cells)	inhibitor	EAE	C57BL/6	Inhibition of antibody production specific for myelin oligodendrocyte glycoprotein (MOG) and suppression of chronic EAE induced by MOG in susceptible mice can be elicited by MOG-Ig gene therapy.	Tolerance induction is an important way of modulating the immune response in an antigen-specific manner to potentially hinder or prevent the progression of the disease.	15093551	Details
Mbp	MBP-Ig gene therapy(retrovirally transduced B cells)	inhibitor	EAE	B10.PL	We observed a delayed disease onset and/or decreased severity in Ac1-11 induced EAE.	Tolerance induction is an important way of modulating the immune response in an antigen-specific manner to potentially hinder or prevent the progression of the disease.	15093551	Details
MBTPS1	fingolimod (FTY720)	inhibitor	MS	N/A	We found that TCF7 expression was decreased in T cells from untreated RRMS patients (T-RRMS) compared with T cells from healthy controls (T-CTL) in both ex vivo isolated and in vitro-activated T cells. To assess whether FTY720 upregulates TCF7 expression in T cells from RRMS patients, we activated T-RRMS cells in the presence or absence of FTY720 and found higher TCF7 expression in FTY720-treated T-RRMS cells .Patients treated with FTY720 showed a significant reduction in circulating CD4 T cells.Activation of T cells in presence of FTY720 showed a less inflammatory phenotype with reduced production of IFN-γ and GZMB.	This decreased effector phenotype of FTY720-treated T cells was dependent on the upregulation of TCF-1.FTY720-induced TCF-1 downregulated the pathogenic cytokines IFN-γ and GZMB by binding to their promoter/enhancer regions and mediating epigenetic modifications.	26714756	Details
Il4	IL-4 DNA vaccination	activator	MS	female SJL/J, BALB/c, and C57BL/6 mice	There is a significant decrease in the mean disease scores at several time points of mice covaccinated with both the IL-4 and PLP139–151 plasmids compared to the controls. There is also a decrease in the incidence of disease and mean peak disease severity with the covaccine.	IL-4 expressed from the naked DNA is secreted and acts locally on autoreactive T cells via activation of STAT6 to shift their cytokine profile to T helper 2.	11485734	Details
MBP	attenuated strains of vaccinia virus genetically engineered to contain the entire coding sequence for human MBP (vT15)	activator	EAE	C. jacchus marmosets	The onset of clinical EAE after immunization (pi) was markedly delayed in vT15-vaccinated animals compared to vAbT249-vaccinated controls. Proliferative responses against MBP but not against vaccinia antigens or phytohemagglutinin were suppressed in protected animals.	Development of attenuated live viruses carrying genes for myelin antigens could be useful for induction of immunologic tolerance and for modulation of autoimmune demyelination.	9394784	Details
ERVW-1	Efavirenz (NNRTI)	inhibitor	MS	Caucasian	Only Efavirenz (NNRTI) decreased the expression of MSRV/HERV-Wenv at the highest concentration.Similarly, HERV-W/HERV-WEnv protein showed by FC a trend of reduction in the presence of 1 μM of combined drugs.	Activation of autoimmune processes in MS results from the interaction of genetic and environmental factors.An additional risk factor that has been identified is the expression of human endogenous retroviruses (HERVs) of the HERV-W family.	30740110	Details
Ms4a1	ocrelizumab	inhibitor	EAE	C57BL / 6	Compared with naive mice, B cell repletion occurred overall faster and more simultaneously throughout the various compartments in the context of an active immunization.After the last anti-CD20 treatment, B cells proliferated in spleen and lymph nodes.Preventive anti-CD20 treatment reduced the severity of MOG protein1–117-induced EAE.Repletion of B cells in purely T cell-mediated EAE dampened the preceding disease exacerbation mediated by anti-CD20 treatment.	systemic anti-CD20 reduced the frequency of B cells in bone marrow, lymph nodes, and the spleen;abrogation of potent B cell APC function.	30194232	Details
Csf1	GW2580	inhibitor	EAE	Dark agouti (DA)	A delay in the appearance of the neurological disability was observed in the EAE + GW2580 group. A significant reduction of the severity of the disease was observed in the EAE + GW2580 group.The EAE + GW2580 animals did not show any relapse phase and after the acute phase, they were recovering till the 18 DPI, last day of the experiment. A decrease was observed in the EAE + GW2580 groups from 2 DPI compared to the GW2580 animals, which is the same profile of the body weight loss observed in the EAE group but less severe, in close correspondence with the evolution of the symptoms of the disorder, which is followed by a recovery.	The tyrosine kinase activity of CSF1R was inhibited by the oral administration of GW2580. GW2580 is a highly selective inhibitor of the c-FMS kinase, and through this pathway, this small molecule blocks CSF1 signaling.	27846891	Details
Il10	amyloid fibrils	activator	EAE	C57BL / 6 mice	In gain-of-function experiments, B-1a cells, adoptively transferred to μMT mice with EAE, restored their therapeutic efficacy when Amylin 28–33 was administered.Stimulation of adoptively transferred bioluminescent MΦs and B-1a cells by amyloid fibrils resulted in rapid trafficking of both cell types to draining lymph nodes.Analysis of gene expression indicated that the fibrils activated the CD40/B-cell receptor pathway in B-1a cells and induced a set of immune-suppressive cell-surface proteins, including BTLA, IRF4, and Siglec G.These mechanisms culminate in reduction of paralytic signs of EAE.	The fibrils activate B-1a cells and F4/80+ MΦs, resulting in their migration to the lymph nodes, where IL-10 and cell-surface receptors associated with immune-suppression limit antigen presentation and T-cell activation.	26621719	Details
Il27	IL-27	activator	EAE	female C57BL/6 mice	Animals that received IL-27-treated DLN cells showed significantly delayed onset of disease, reduced severity, and enhanced recovery compared with the control group.Release of IL-17 from Ag-specific cells was significantly suppressed in the IL-27-treated group (Fig. 4D).	IL-27 significantly inhibited both nonpolarized and IL-23-driven IL-17 production by myelin-reactive T cells thereby suppressing their encephalitogenicity in adoptive transfer EAE.	17709543	Details
Mog	DNA vaccines encoding MOG(91-108)	activator	EAE	LEW.1AV1, LEW.1N,DA rats	In all investigated rat strains DNA vaccination suppressed clinical signs of EAE.In CNS-derived lymphocytes, Fas ligand expression was down-regulated in DNA-vaccinated rats compared with controls.However, MOG-specific IgG2b responses were enhanced after DNA vaccination.	Deoxyribonucleic acid vaccination can induce Ag-specific CD4+, CD8+ and CTL responses that are protective against infectious disease. DNA vaccination can also protect from autoimmune disease.EAE is an animal model of multiple sclerosis (MS) and can be induced in rodents by myelin oligodendrocyte glycoprotein (MOG).	12574345	Details
Foxp3	CAR/FoxP3-engineered T regulatory cells	activator	EAE	female C57BL/6 mice	Efficiently suppressed ongoing inflammation leading to diminished disease symptoms.	The engineered Tregs expressed both CAR and FoxP3, and in assays testing their function they significantly decreased T cell proliferation even in the presence of LPS-stimulated macrophages that are thought to take part in the transformation of Tregs into Th17 effector cells due to their production of activating cytokines.	22647574	Details
Nfe2l2	DMI	activator	EAE	C57BL / 6,SJL / J	DMI ameliorated disease severity in the chronic C57BL/6 EAE model.Strikingly, DMI also exhibited a therapeutic effect on alleviating severity of relapse in the relapsing-remitting SJL/J EAE model.	Further analysis of the cellular and molecular mechanisms revealed that DMI mitigated BBB disruption, inhibited MMP3/MMP9 production, suppressed microglia activation, inhibited peripheral Th1/Th17 differentiation, and repressed the CNS infiltration of Th1 and Th17 cells.	32349768	Details
Ifng	IFN-γ primed WJ-MSCs	activator	EAE	female C57BL/6 mice	Leukocyte infiltration and symptoms were significantly reduced in IFN-γ primed WJ-MSCs treated group compared to other groups.These cells showed significantly reduced proliferation and increased Treg cells as well as decreased secretion and gene expression of inflammatory cytokines in EAE mice.	IFN-γ may be used to stimulate the immunomodulatory property of WJ-MSCs in clinical situations.	27697286	Details
Il33	IL-33	activator	EAE	female SJL rat	IL-33 expands ILC2s, drives a Th2 response, and diminishes clinical signs of EAE in females.	Reduced expression of IL-33 leading to a diminished ILC2 response in females underlies sex-dimorphic EAE susceptibility, IL-33 treatment of SJL females should confer protection by activating ILC2s and shifting the pathogenic anti-myelin response to one that is Th2 skewed.	29378942	Details
Ctla4	AdCTLA (CTLA4-Ig fusion protein)	inhibitor	EAE	Biozzi ABH (H2dq1) mice	The development and intensity of lesion load is delayed and reduced, respectively, in mice receiving AdCTLA and thus correlates well with the clinical profile observed.	In contrast to some of the stimulating/agonist capabilities of mAb specific for CTLA4, CTLA4-Ig fusion proteins (CTLA4-Ig) appear to act as CD28 antagonists and prevent co-stimulation in vitro and inhibit in vivo T cell priming in a variety of immunological diseases.	9862327	Details
Plp1	retroviral vectors SNV-MPL with PLP 100-154 coding sequence	activator	EAE	female (BALB/c × SJL) F1 mice	Adoptive transfer of syngeneic B cells expressing the PLP encephalitogenic determinant into normal, naive, genetically susceptible mice induced PLP-specific unresponsiveness and completely protected the majority of the animals from EAE induction.The remaining animals had a delayed disease onset and/or lower disease severity.	If normal, resting B cells could be genetically modified to constitutively express a particular autoantigen, they would continuously down-regulate all T-cell clones specific for this antigen.	11159513	Details
Cnr2	HU‐308	activator	EAE	C57BL/6	HU‐308 significantly reduced the peak severity and cumulative clinical score of EAE.Histological examination of the spinal cords was performed at day 17 postimmunization (PI).Compared to vehicle control, HU‐308 aused a dramatic reduction of leukocyte infiltration in spinal cord. Luxol fast blue staining also revealed less extensive demyelination in HU‐308‐treated mice than in controls.	Activation of CB2R ameliorate EAE through suppressing key components of the inflammatory process and reducing Th17 differentiation, immune cell accumulation, and microglia activation in the CNS.	25417929	Details
Il2	DAB389IL-2	inhibitor	EAE	female Lewis rats	DAB(389)IL-2 inhibited infiltration of CD4(+), CD8(+), CD25(+) and TCR αβ(+) associated mononuclear cells and inflammatory macrophages in the spinal cord on day 13 post-immunization, at the peak of disease.Gene expression study showed that DAB(389)IL-2 treatment suppressed TNF-α and IFN-γ as well as IL-10 cytokine gene expression in the spinal cord of rats with EAE on day 13.DAB(389)IL-2 in vitro treatment suppressed cytotoxicity of MBP-activated T cells from rats with EAE against oligodendrocytes in culture by 66%.Astrocytes were less targeted by MBP activated T cells in vitro.	DAB(389)IL-2 directly targets CD4(+) and CD25(+) (IL-2R) T cells and effector T cell function and also indirectly suppresses the activation of macrophage CD169(+) (ED3(+)) and microglia CD11b/c (OX42(+)) populations in the CNS.	23872438	Details
Igf1	IGF-I	activator	EAE	male Lewis rats	IGF-I produced significant reductions in numbers and areas of demyelinating lesions.Relative mRNA levels for myelin basic protein, proteolipid protein (PLP), and 2',3'-cyclic nucleotide 3'-phosphodiesterase in lesions of IGF-I-treated rats were significantly higher than they were in placebo-treated rats. PLP mRNA-containing oligodendroglia also were more numerous and relative PLP mRNA levels per oligodendrocyte were higher in lesions of IGF-I-treated rats. Finally, a significantly higher proportion of proliferating cells were oligodendroglia-like cells in lesions of IGF-I-treated rats.	Several lines of evidence suggest that insulin-like growth factor I (IGF-I) might be useful in reducing myelin breakdown and promoting myelin regeneration in demyelinating diseases. IGF-I promotes the survival of oligodendroglia and the formation of myelin sheaths in vitro. The content of myelin also is increased in the central nervous system of transgenic mice that overexpress IGF-I.	7541143	Details
Il23a	IL23R-CHR	inhibitor	EAE	female C57BL/6 mice	EAE mice treated with hIL23R-CHR displayed a lower incidence of disease compared to CsA treatment.	The present in vivo study further demonstrated that hIL23R-CHR inhibited murine Th17 cell development by down regulating IL-17 gene expression and protected mice against the development of experimental autoimmune encephalomyelitis (EAE) through suppression of CNS inflammation and pro-inflammatory cytokine production.	25263529	Details
Arg1	ABH	inhibitor	EAE	C57BL/6 (B6) mice	ABH treatment not only delayed the onset but also reduced the severity of the disease.	ABH is effective in inhibiting arginase activities in the central nervous system.	12941151	Details
Plp1	PLPfl-transduced BM	activator	EAE	SJL female mice	The group that received BMT expressing the PLPfl construct was completely protected from disease induction. We observed massive perivascular inflammatory infiltration in the control group but not in the PLPfl-transduced BM recipients.Using this form of the therapy, we were able to block EAE progression completely in mice reconstituted with BM expressing PLPfl construct and ameliorate symptoms even after the disease symptoms had emerged.	Bone marrow (BM) or blood stem cell transplantation has been shown to be effective in treating severe and refractory autoimmune diseases.	16219491	Details
Gnpat	lovastatin	activator	EAE	female Lewis rats	Lovastatin treatment reduced the effect produced by EAE disease on the repression of expression of transcripts encoding peroxisomal proteins.Lovastatin treatment significantly up-regulated the expression of catalase, acyl CoA oxidase DHAP-AT and PEX6 in EAE Lewis rats compared with untreated counterparts.	At the mRNA level, enhanced stability or increased transcriptional activity.	15353207	Details
Tgfb1	CNS-homing gene delivery/therapy vectors based on avirulent Semliki Forest virus (SFV) expressing either native or mutant transforming growth factor beta 1 (TGF-beta1)	activator	EAE	Balb/c mice	Both vectors, when given intraperitoneally to EAE mice significantly reduced disease severity compared to untreated mice.	Immunomodulation by neurotropic viral vectors may offer a promising treatment strategy for autoimmune CNS disorders.	17316567	Details
H2-Ab1	monoclonal antibodies directed against the IA antigens of the MHC	inhibitor	EAE	F1 (SJL/J X BALB/c) mice	Antibody directed against I-As, was successful in preventing disease when therapy was begun either at the time of immunization with antigen, or following passive transfer of MBP-sensitized T cells. The mice had a delayed onset, and reduced incidence in the development of EAE.	Susceptibility to autoimmune disease is linked closely to the IR genes of the MHC. In vivo administration of antibody to the immune response gene products (anti-IA antibody) is effective in preventing and mitigating the course of a number of experimental autoimmune diseases including EAE.	3497972	Details
IFNB1	IFN-β-1a	activator	MS	Caucasian patients	We identified 121 genes that were significantly up- or downregulated compared with baseline, with stronger changed expression at 1 week after start of therapy. Eleven transcription factor-binding sites (TFBS) are overrepresented in the regulatory regions of these genes, including those of IFN regulatory factors and NF-κB.	Interferon-b (IFN-b) is currently the most established treatment for controlling the exacerbations in relapsing–remitting MS and several studies have confirmed its clinical benefit.IFN-b is a natural human pleiotropic cytokine with antiproliferative and immunomodulatory activities that is produced by various cell types including fibroblasts and macrophages. It exerts its biological effects by binding to specific cell surface receptors.	20956993	Details
Lif	HSV-LIF vector	activator	EAE	SJL/J mice	The HSV-LIF significantly ameliorated the EAE and contributed to a higher number of oligodendrocytes in the brains when compared to untreated mice.The HSV-LIF therapy also induced favorable changes in the expression of immunoregulatory cytokines and T-cell population markers in the CNS during the acute disease.	Herpes simplex virus type 1 (HSV-1) has properties that can be exploited for the development of gene therapy vectors. LIF is a cytokine that has the potential to limit demyelination and oligodendrocyte loss in CNS autoimmune diseases and to affect the T-cell mediated autoimmune response.	23700462	Details
Mbp	I-AS protein plus MBP 91-103 complex	inhibitor	EAE	female SJL/J mice	I-As protein were effective in preventing experimental allergic encephalomyelitis and prevented mortality and significantly reduced paralysis induced by immunization with the encephalitogenic proteolipoprotein peptide and prevented the development of inflammatory lesions characteristic of experimental allergic encephalomyelitis.	Experimental allergic encephalomyelitis is a T-cell-mediated, major histocompatibility complex (MHC) class II gene-linked autoimmune demyelinating disease of the central nervous system.	1722335	Details
IL4	HSV-1-derived vector containing the IL-4 gene	activator	EAE	mice	We found the following in treated mice: (1) delayed EAE onset, (2) a significant decrease in clinical score, (3) a significant decrease in perivascular inflammatory infiltrates and in the number of macrophages infiltrating the CNS parenchyma and the submeningeal spaces, and (4) a reduction in demyelinated areas and axonal loss.	CNS cytokine delivery with HSV-1 vectors is feasible and might represent an approach for the treatment of demyelinating diseases.	9853527	Details
N/A	N/A	N/A	N/A	N/A	N/A	N/A	24024893	Details
Cnr1	rolipram	activator	EAE	Lewis rats	supresses EAE in different species,attenuated clinical decline, reduced motor inhibition, and normalized CB1 receptor gene expression in the basal ganglia.	an inhibitor of type IV phosphodiesterase	16242629	Details
Cnr1	AM404,arvanil,OMDM2	inhibitor	EAE	Lewis rats	We found that the administration of the endocannabinoid transport inhibitors ,AM404 and arvanil,was effective at reducing the magnitude of the neurological decline in EAE rats . OMDM2 , another endocannabinoid transport inhibitor also reduced neurological decline in EAE rats.	Based on the occurrence of reduced endocannabinoid levels in the brain of EAE rats,enhancing endocannabinoid activity by inhibiting endocannabinoid transport is beneficial to reduce clinical injury in EAE rats.	16242629	Details
Trpv1	AM404,arvanil	activator	EAE	Lewis rats	We found that the administration of the vanilloid TRPV1 receptor agonists,AM404 and arvanil , was effective at reducing the magnitude of the neurological decline in EAE rats .	capability to activate TRPV1 receptors	16242629	Details
NRG1	rhGGF2	activator	EAE	Female SJL/J mice	In comparison to control groups, rhGGF2 treatment , consistently resulted in an improved clinical course, a reduction in relapse rate, lessened CNS pathology, and an increase in the amount of CNS remyelination.	RhGGF2 exerted a direct effect on either the induction or effector phase of the disease through a reduction in cell activation (lymphocytic or microglial) or modulation of cell traffic at the blood-brain barrier.And it's correlated with increased mRNA expression of myelin basic protein exon 2, a marker for remyelination, and with an increase in the CNS of the regulatory cytokine, interleukin 10, at both the RNA and protein levels.	9707607	Details
IFNG	IFN-β	inhibitor	MS	372 ambulatory patients with relapsing-remitting multiple sclerosis (MS)	the identification of a substantial reduction in the relapse rate and new demyelinating lesions on MR.	The mechanism of action of IFN-β appears likely to be related to its in vitro effect in blocking the stimulation of MHC molecules by IFN-γ.	11902592	Details
Sod3	AAV-ECSOD	activator	EAE	DBA/1J mice	These findings are suggestive of the long-term protective effect of antioxidant gene therapy against degeneration of the optic nerve induced by chronic EAE.Viral-mediated delivery of antioxidant genes provides long-lasting suppression against neuronal and axonal loss associated with permanent visual disability in patients with multiple sclerosis.	Reactive oxygen species (ROS) such as superoxide, hydrogen peroxide, nitric oxide, and peroxynitrite are mediators of demyelination and disruption of the blood-brain barrier (BBB) in EAE.ECSOD has been shown to offer central nervous system (CNS) neuroprotection.	18055782	Details
Cat	AAV-CAT	activator	EAE	DBA/1J mice	These findings are suggestive of the long-term protective effect of antioxidant gene therapy against degeneration of the optic nerve induced by chronic EAE.Viral-mediated delivery of antioxidant genes provides long-lasting suppression against neuronal and axonal loss associated with permanent visual disability in patients with multiple sclerosis.	Reactive oxygen species (ROS) such as superoxide, hydrogen peroxide, nitric oxide, and peroxynitrite are mediators of demyelination and disruption of the blood-brain barrier (BBB) in EAE.Cellular defenses against ROS include catalase.	18055782	Details
Cxcl12	Aminoguanidine (AG),a selective inhibitor of iNOS activity	activator	EAE	DA rats immunized to develop EAE	AG mitigated EAE and upregulated CXCL12 gene expression in SCH and MBV .Increased staining with anti-CXCL12 antibodies was determined .CXCL12-positive areas in the AG-treated group spread from cell processes deeper into the spinal cord parenchyma and structures of blood vessels were positive for CXCL12.	In vivo inhibition of iNOS activity sustains CXCL12 gene and protein expression and protects rats from EAE, while in vivo donation of NO inhibits CXCL12 gene expression.	23732617	Details
F2r	PAR-1 antagonist, FR171113 and SCH79797 dihydrochloride, a selective inhibitor of PAR-1	inhibitor	late/chronic EAE	wild-type mice and NR4A2 cKO mice	Cumulative disease burden were significantly suppressed in both wild-type mice and NR4A2 cKO mice.	CD4+ memory T cells and CD8+ T cells have been reported as mediating cytotolytic effects via granzyme B release.	26436530	Details
Ifnb1	Interferon-β (IFN-β)	activator	EAE	C57BL/6 female mice	Therapeutic administration of MSC-VP/IFN-β reduced the severity of disease in EAE.MSCs-VP/IFN-β downregulated the levels of IL-17 expression and upregulated the characteristic anti-inflammatory cytokine i.e., IL-10 and Treg related transcription factor, Foxp3. A robust increase in anti-inflammatory gene expression, i.e., IL-10 and downregulation of inflammatory cytokines, IL-17, was observed in mice treated with MSCs-VP/IFN-β when compared with MSCs. MSCs-VP/IFN-β treated groups increased the frequency of Treg cells.	Interferon-β (IFN-β) is commonly used as a disease modifying drug for the treatment of Relapseremitting multiple sclerosis (RR-MS). The expression of TGF-β and IL-10 under the control of IFN-β may be one of the most important mechanisms which play a critical role in the induction of Treg cells in EAE mice.	27373971	Details
FGF2	human broblast growth factor (FGF)-II gene(TH:bFGF vector)	activator	EAE	C57BL/6 mice	TH:bFGF-treated mice showed a lower number of T cells and macrophages (butalso of inammatory perivascular inltrates) both in theCNS parenchyma and in the leptomeningeal space and a signicant increase of oligoden-drocyte precursors (platelet derived growth factor-receptor α(PDGFRα)+cells) in areas of demyelination andaxonal loss.A signicant decrease of the per-centage of spinal cord demyelination and axonal loss was also observed in TH:bFGF-treated mice. A signicant increase of proteolipidprotein (PLP)-expressing oligodendrocytes was also measured in TH:bFGF-treated mice .Neuropathological ndings indicate that the sustained disease-ameliorating effect observed after the treatment with the TH:bFGF vector was associated with a signi-cant decrease of the extent of CNS demyelination andaxonal loss.	We attribute the disease-ameliorating effect to the FGF-II-mediated recruitment into demyelinating areas of oligodendrocyte precursors located in close vicinity to or surviving within demyelinating lesions which, in turn, differentiated into myelin-forming cells.	11509953	Details
Ephb2	Broad-spectrum tyrosine kinase inhibitors Dasatinib and Vandetanib	inhibitor	EAE	mice (MGI ID 3603008)	EAE score was greatly reduced after two weeks of oral gavage of Vandetanib and Dasatinib.Vandetanib was more effective than Dasatinib in terms of EAE treatment, which may be owing to the stronger inhibition of proinflammatory gene induction by Vandetanib compared with Dasatinib. There was significantly less Th17 cells brain infiltration after Vandetanib and Dasatinib treatment, and Th17 and Th1 cell polarization were both significantly reduced in the spleen after treatment with these inhibitors.	inhibit EPHB2 kinase activity and EPHB2-mediated TAGAP phosphorylation	32312989	Details
Mbp	hmTAP (synthetic human multitarget autoantigen protein)	inhibitor	PLP139-151–induced EAE	highly specific line T cells raised from PLP139-151–primed and MOG35-55–primed SJL/J and C3H.SW mice	Intraperitoneal injections with hmTAP had a strong suppressive effect on PLP139-151–induced EAE, not only at the initial phase but also at the chronic stage of the disease.The effect of intravenous administration of hmTAP on PLP139-151–induced EAE in SJL/J mice was even more dramatic.	Abrogation is associated with inhibition of encephalitogenic T cells.	12093891	Details
Plp1	hmTAP (synthetic human multitarget autoantigen protein)	inhibitor	PLP139-151–induced EAE	highly specific line T cells raised from PLP139-151–primed and MOG35-55–primed SJL/J and C3H.SW mice	Intraperitoneal injections with hmTAP had a strong suppressive effect on PLP139-151–induced EAE, not only at the initial phase but also at the chronic stage of the disease.The effect of intravenous administration of hmTAP on PLP139-151–induced EAE in SJL/J mice was even more dramatic.	Abrogation is associated with inhibition of encephalitogenic T cells.	12093891	Details
Mog	hmTAP (synthetic human multitarget autoantigen protein)	inhibitor	PLP139-151–induced EAE	highly specific line T cells raised from PLP139-151–primed and MOG35-55–primed SJL/J and C3H.SW mice	Intraperitoneal injections with hmTAP had a strong suppressive effect on PLP139-151–induced EAE, not only at the initial phase but also at the chronic stage of the disease.The effect of intravenous administration of hmTAP on PLP139-151–induced EAE in SJL/J mice was even more dramatic.	Abrogation is associated with inhibition of encephalitogenic T cells.	12093891	Details
Tnfsf4	pOX40-TRAIL/ND(DNA encoding OX40-TRAIL cloned into the pND vector)	inhibitor	EAE	female C57BL/6 mice	decreased severity of EAE and reduced inflammatory cell infiltrates beneath the meninges	block pro-inflammatory signaling,inhibite pathogenic T cells	21732666	Details
Plp1	a syngeneic fibroblast line transduced with a retroviral vector designed to encode proteolipid protein (101-157) targeted for secretion	activator	EAE	female SJL/J mice	Animals receiving PLP-secreting fibroblasts showed significant reductions of clinical signs.Histological studies in these mice showed either no inflammatory infiltrates or scattered perivascular or subarachnoid infiltrates, and no demyelination.The injection of PLP-secreting fibroblasts reduces the frequency and severity of EAE relapses and ameliorates the pathological destruction.Treatment of EAE mice with PLP-secreting cells results in the generation of antiinflammatory cytokines, in contrast with untreated EAE mice, which have elevated levels of IL-2 and IFN-γ.	This strategy was devised to provide a systemic, antigen-specific signal to pathogenic T cells in the absence of costimulation and, hence, render them anergic and this antigen-specific therapy acts by a cytokine-induced pathway.	14991817	Details
Hdac1	trichostatin A (TSA)	inhibitor	EAE	C57BL/6 female mice	Trichostatin A (TSA) reduces spinal cord inflammation, demyelination, neuronal and axonal loss and ameliorates disability in the relapsing phase of experimental autoimmune encephalomyelitis (EAE).TSA up-regulates antioxidant, anti-excitotoxicity and pro-neuronal growth and differentiation mRNAs.TSA also inhibits caspase activation and down-regulates gene targets of the pro-apoptotic E2F transcription factor pathway.In splenocytes, TSA reduces chemotactic, pro-Th1 and pro-proliferative mRNAs.	Trichostatin A (TSA) is an inhibitor of histone deacetylase (HDAC) and histone deacetylase (HDAC) enzymes repress genes via condensation of the nucleosome and interactions with transcription factors.	15885809	Details
Lif	lentiviral vectors (LVs) used to achieve stable expression and secretion of LIF in the CNS	inhibitor	EAE	C57Bl/6J mice	CNS-targeted expression of LIF significantly reduced demyelination in a murine model of MS. In addition, local expression of LIF ameliorated clinical symptoms with enhanced efficacy compared to systemic treatment with recombinant protein.	N/A	20068552	Details
Mir219a-2	miR-219	activator	EAE	female C57BL/6 mice	miR-219 augmented the recovery of neurological functions in EAE Mice and exhibited a significant improvement in motor function.It appeared restoration of MBP expression in the lesions of lumbar spinal cords, which exhibit the prominent demyelinating lesions in EAE , and reduction of the demyelinated regions.	the presence of a higher number of CC1+ or Plp1+ OLs in the spinal lesions from miR-219-mimic-treated mice,miR-219 mimic acts as a remyelination-promoting agent to improve the clinical symptoms of EAE.	28350989	Details
Gsn	LV-GSN	inhibitor	EAE	Lewis male rats	GSN administration can delay the onset and decrease the severity of EAE.	LV-GSN and vitamin D3 supplementation delays the onset of EAE and reduces inflammation.	28377587	Details
Malt1	mepazine	inhibitor	EAE	Male mice	Treatment with mepazine reduces experimental autoimmune encephalomyelitis (EAE) severity	Reduced central nervous system demyelination, axonal damage and inflammatory cell infiltration and cytokine expression in mepazine-treated mice	25043939	Details
Hspd1	pVAXhsp65	inhibitor	EAE	C57BL/6	These results indicate that hsp65, administered as a DNA vaccine, was not therapeutic for EAE	Although pVAXhsp65 was immunogenic for mice with EAE and downmodulated specific cytokine induction byMOG, therapy was not able to decrease clinical severity nor tomodify immunologic parameters in the CNS	24439542	Details
Il4	IL-4	inhibitor	EAE	Mus musculus	Protection from autoimmune encephalomyelitis and multiple sclerosis has been achieved with IL-4 therapy	potent anti-inflammatory properties	16169606	Details
Il4	Semliki Forest Virus Recombinant Particles wiwth IL-4	inhibitor	EAE	Balb/c	the mice showed a significant biological response when treated i.n. with recombinant SFV particles and that such particles administered by the i.n. route have potential as a noninvasive vector for protein delivery to the CNS	N/A	14664790	Details
Il4	HSV-1-derived vector containing the gene of the anti-inflammatory cytokine IL-4	inhibitor	EAE	BALB/c	Compared to controls, mice affected by experimental autoimmune encephalomyelitis (EAE) and i.c. injected with an HSV-1-derived vector containing the gene of the anti-inflammatory cytokine IL-4 showed a significant amelioration of clinical and pathological EAE signs	non-toxic system to deliver cytokines within the central nervous system (CNS)	10854655	Details
CCR6	fumaric acid esters	inhibitor	MS	Homo sapiens	These data collectively define a direct link between fumaric acid ester treatment and hypermethylation of the MIR-21 locus in both CD4 and CD8 T cells and suggest that the immunomodulatory effect of fumaric acid esters in multiple sclerosis is at least in part due to the epigenetic regulation of the brain-homing CCR6+ CD4 and CD8 T cells.	the upregulation of miR-21 transcripts and CCR6 expression was inhibited	30698680	Details
GAPVD1	IFN-β	inhibitor	MS	Homo sapiens	The results show that the GAPVD1 expression level and rs2291858 genotype probably affect the response to IFN-β in patients with MS.	affect the response to IFN- β in patients with MS.	33548618	Details
TNF	Interferon beta-1b	inhibitor	MS	Homo sapiens	IFN-1b decreases the spontaneous expression of two proinflammatory cytokines	IFN-1b decreases the spontaneous expression of two proinflammatory cytokines	10371521	Details
IFNG	Interferon beta-1b	inhibitor	MS	Homo sapiens	IFN-1b decreases the spontaneous expression of two proinflammatory cytokines	IFN-1b decreases the spontaneous expression of two proinflammatory cytokines	10371521	Details
IFNB1	IFN-β	inhibitor	RRMS	American	the higher dosed, more frequently administered IFN-尾 1a Rebif when compared to IFN-尾 1a Avonex has more potent immunomodulatory effects	The STAT1-inducible genes IP-10 and caspase 1 were significantly increased with Rebif compared to Avonex.	21658727	Details
IFNB1	IFN-β	inhibitor	MS	Danes	spontaneous expression of interferon-尾-inducible genes in peripheral blood mononuclear cells from untreated multiple sclerosis patients and treatment with interferon-尾 are associated with reduced myelin basic protein-induced T-cell responses. Reduced myelin basic protein-induced CD4+ T-cell autoreactivity in interferon-尾-treated multiple sclerosis patients may be mediated by monocyte-derived interleukin-10.	found an association of high expression levels of interferon-尾-inducible genes with an increased expression of interleukin-10 and a milder disease course in untreated multiple sclerosis patients	25738751	Details
HOTAIR	VD	inhibitor	MS	Iranian	expression of HOTAIR and ANRIL is probably not affected by VD and/or inflammation in THP-1 cells in vitro	potent inflammatory milieu	29030863	Details
Hotair	VD	inhibitor	EAE	C57BL/6	a role of Hotair in neuroinflammatory and neurodegenerative processes underlying MS in a tissue-specific manner	neuroinflammatory and neurodegenerative	29030863	Details
CDKN2B-AS1	VD	inhibitor	MS	Iranian	expression of HOTAIR and ANRIL is probably not affected by VD and/or inflammation in THP-1 cells in vitro	potent inflammatory milieu	29030863	Details
Gm12610	VD	inhibitor	EAE	C57BL/6	Implication of Hotair but not Anril in the pathogenesis of EAE	epigenetic mechanisms	29030863	Details
MYC	VD	inhibitor	MS	Iranian	The expression of the VDR and c-Myc genes, two well-known early response genes to VD, were significantly induced after 24 hr of 100 nmol/ml VD exposure	epigenetic mechanisms	29030863	Details
VDR	VD	inhibitor	MS	Iranian	The expression of the VDR and c-Myc genes, two well-known early response genes to VD, were significantly induced after 24 hr of 100 nmol/ml VD exposure	epigenetic mechanisms	29030863	Details
Nfe2l2	TFM-735	inhibitor	EAE	C57BL/6 J	TFM-735 is a potent Nrf2 inducer that inhibits inflammatory cytokine production and disease progression in mice with EAE and that TFM-735 is a promising therapeutic agent for MS	inhibits inflammatory cytokine production and disease progression	28246026	Details
Nqo1	TFM-735	inhibitor	EAE	C57BL/6 J	the expression of the Nrf2 target gene Nqo1 increased in the brain and spleen, disease severity was ameliorated	N/A	28246026	Details
Mbp	MBP-PE 40	inhibitor	EAE	C57BL	A chimeric protein such as MBP-PE40 presents a novel prototype of chimeric proteins, composed of antigen/peptide-toxin, that could prove to be an efficient and specific immunotherapeutic agent for autoimmune diseases in which a known antigen is involved	cytotoxic to various anti-MBP T cells	10424450	Details
EOMES	glatiramer acetate (GA)	inhibitor	MS	Russians	The biallelic combinations including EOMES, CLEC16A, IL22RA2, PVT1, TYK2, CD6, IL7RA and IRF8 genes were associated with response to GA with increased significance level	epistasic interactions or additive effects	29095108	Details
CLEC16A	glatiramer acetate (GA)	inhibitor	MS	Russians	The biallelic combinations including EOMES, CLEC16A, IL22RA2, PVT1, TYK2, CD6, IL7RA and IRF8 genes were associated with response to GA with increased significance level	epistasic interactions or additive effects	29095108	Details
IL22RA2	glatiramer acetate (GA)	inhibitor	MS	Russians	The biallelic combinations including EOMES, CLEC16A, IL22RA2, PVT1, TYK2, CD6, IL7RA and IRF8 genes were associated with response to GA with increased significance level	epistasic interactions or additive effects	29095108	Details
PVT1	glatiramer acetate (GA)	inhibitor	MS	Russians	The biallelic combinations including EOMES, CLEC16A, IL22RA2, PVT1, TYK2, CD6, IL7RA and IRF8 genes were associated with response to GA with increased significance level	epistasic interactions or additive effects	29095108	Details
TYK2	glatiramer acetate (GA)	inhibitor	MS	Russians	The biallelic combinations including EOMES, CLEC16A, IL22RA2, PVT1, TYK2, CD6, IL7RA and IRF8 genes were associated with response to GA with increased significance level	epistasic interactions or additive effects	29095108	Details
CD6	glatiramer acetate (GA)	inhibitor	MS	Russians	The biallelic combinations including EOMES, CLEC16A, IL22RA2, PVT1, TYK2, CD6, IL7RA and IRF8 genes were associated with response to GA with increased significance level	epistasic interactions or additive effects	29095108	Details
IRF8	glatiramer acetate (GA)	inhibitor	MS	Russians	The biallelic combinations including EOMES, CLEC16A, IL22RA2, PVT1, TYK2, CD6, IL7RA and IRF8 genes were associated with response to GA with increased significance level	epistasic interactions or additive effects	29095108	Details
IL7R	glatiramer acetate (GA)	inhibitor	MS	Russians	The biallelic combinations including EOMES, CLEC16A, IL22RA2, PVT1, TYK2, CD6, IL7RA and IRF8 genes were associated with response to GA with increased significance level	epistasic interactions or additive effects	29095108	Details
TNF	Lipopolysaccharide	inhibitor	EAE	C57BL6	Consistently led to a delayed onset of disease but not to a reduction in disease severity	affects antigen presentation and may modulate the expression of inflammatory regulators that impact the autoimmune disease course	17055066	Details
TGFB1	Lipopolysaccharide	inhibitor	EAE	C57BL6	Consistently led to a delayed onset of disease but not to a reduction in disease severity	affects antigen presentation and may modulate the expression of inflammatory regulators that impact the autoimmune disease course	17055066	Details
IFNB1	Lipopolysaccharide	inhibitor	EAE	C57BL6	Consistently led to a delayed onset of disease but not to a reduction in disease severity	affects antigen presentation and may modulate the expression of inflammatory regulators that impact the autoimmune disease course	17055066	Details
NOS3	Lipopolysaccharide	inhibitor	EAE	C57BL6	Consistently led to a delayed onset of disease but not to a reduction in disease severity	affects antigen presentation and may modulate the expression of inflammatory regulators that impact the autoimmune disease course	17055066	Details
Rorc	ATRA and calcitriol	inhibitor	EAE	C57BL6	The expression of FOXP3 and TGF-å°¾ genes in the splenocytes of combination-treated and calcitriol alone-treated mice was significantly increased compared to vehicle group (P< 0.05).	N/A	27996890	Details
Il17a	ATRA and calcitriol	inhibitor	EAE	C57BL6	The expression of FOXP3 and TGF-å°¾ genes in the splenocytes of combination-treated and calcitriol alone-treated mice was significantly increased compared to vehicle group (P< 0.05).	N/A	27996890	Details
Tgfbr1	ATRA and calcitriol	inhibitor	EAE	C57BL6	The expression of FOXP3 and TGF-å°¾ genes in the splenocytes of combination-treated and calcitriol alone-treated mice was significantly increased compared to vehicle group (P< 0.05).	N/A	27996890	Details
Cxcl12	4-Methylumbelliferone (4MU)	inhibitor	EAE	C57BL6	Inhibition of hyaluronan synthesis protects against CNS inflammation.	modulates T-cell responses, and prevents CXCL12 suppression within inflamed and non-inflamed CNS tissue	24973214	Details
Il12a	Interleukin 35 and hepatocyte growth factor	inhibitor	EAE	N/A	It is expected that Interleukine-35 and Hepatocyte Growth Factor genes expressed from MSCs could effectively perform in immunotherapy of Multiple Sclerosis.	anti-inflammatory and remyelination of Interleukine-35 and Hepatocyte Growth Factor properties	29150266	Details
Hgf	Interleukin 35 and hepatocyte growth factor	inhibitor	EAE	N/A	It is expected that Interleukine-35 and Hepatocyte Growth Factor genes expressed from MSCs could effectively perform in immunotherapy of Multiple Sclerosis.	anti-inflammatory and remyelination of Interleukine-35 and Hepatocyte Growth Factor properties	29150266	Details
Rnf128	HINT1/Hsp70	inhibitor	EAE	C57BL6/J，SJL/J	suppressed PLP-induced T cell proliferation by enhancing T cell expression of GRAIL as GRAIL downregulation restored T cell proliferation	HINT1/Hsp70 treatment generated regulatory NK cells characterized by expression of GRAIL.	31362466	Details
TNF	Lipopolysaccharide	inhibitor	EAE	C57BL6	Consistently led to a delayed onset of disease but not to a reduction in disease severity	affects antigen presentation and may modulate the expression of inflammatory regulators that impact the autoimmune disease course	17055066	Details
TNFSF13B	IFN-β	inhibitor	MS	Australian and New Zealand	We conclude BAFF is a good biomarker for IFN-β response	N/A	18715196	Details
Plp1	green tea epigallocatechin-3-gallate (EGCG)	inhibitor	EAE	C57BL6	EGCG increases PLP and Olig1 expression in the cerebral cortex of a mouse model of MS induced by cuprizone	N/A	28984112	Details
Olig1	green tea epigallocatechin-3-gallate (EGCG)	inhibitor	EAE	C57BL6	EGCG increases PLP and Olig1 expression in the cerebral cortex of a mouse model of MS induced by cuprizone	EGCG) might be effective in improving the symptoms and pathological conditions associated with autoimmune inflammatory diseases in several animal models	28984112	Details
IL10	IL10	inhibitor	EAE	SJL/J and CSJLF1/J	This study demonstrates that IL-10 can prevent EAE completely if present at appropriate levels and times during disease induction.	Myelin-reactive T helper 1 cells are induced but nonpathogenic in the IL-10 transgenic mice	10075984	Details
Mbp	combined therapy of vitamins A and C	inhibitor	experimental autoimmune encephalomyelitis	Lewis rats	Our findings suggest that combined therapy of vitamins A and C protect myelin damage via increasing BDNF and MBP levels in the CNS and causes anti-inflammatory, antioxidant and neuroprotective impacts in the EAE model.	N/A	35072933	Details
Bdnf	combined therapy of vitamins A and C	inhibitor	experimental autoimmune encephalomyelitis	Lewis rats	Our findings suggest that combined therapy of vitamins A and C protect myelin damage via increasing BDNF and MBP levels in the CNS and causes anti-inflammatory, antioxidant and neuroprotective impacts in the EAE model.	N/A	35072933	Details
Mt2	MT2	inhibitor	experimental autoimmune encephalomyelitis	C57BL/6 and TgMT mice	the administration of MT1 and MT2 showed a clear trend to decrease the clinical signs, but only the MT2 isoform did it significantly.	N/A	30543238	Details
Akt2	FTY720	inhibitor	experimental autoimmune encephalomyelitis	CD38-deficient	we have shown attenuation ofEAE after treatment with FTY720 or reduced EAE severity in CD38-deficient mice	treatment of MOG-induced EAE with FTY720 impacts the gene expression of the genes that are involved in encephalitogenic immune responses.	27519689	Details
Cnp	Teriflunomide	activator	N/A	Wistar rat	Quantitative RT-PCR after 1d revealed that stimulation of primary rat OPCs with tolerated concentration profiles of teriflunomide led to a significant upregulation of CNPase, TAp73, Mash1/Ascl1, Myrf, Nkx2.2, PLP, and Sox 10 transcript levels	Short-term teriflunomide pulses can efficiently promote oligodendroglial cell differentiation suggesting that young, immature cells could benefit from such stimulation.	29534752	Details
Ascl1	Teriflunomide	activator	N/A	Wistar rat	Quantitative RT-PCR after 1d revealed that stimulation of primary rat OPCs with tolerated concentration profiles of teriflunomide led to a significant upregulation of CNPase, TAp73, Mash1/Ascl1, Myrf, Nkx2.2, PLP, and Sox 10 transcript levels	Short-term teriflunomide pulses can efficiently promote oligodendroglial cell differentiation suggesting that young, immature cells could benefit from such stimulation.	29534752	Details
Myrf	Teriflunomide	activator	N/A	Wistar rat	Quantitative RT-PCR after 1d revealed that stimulation of primary rat OPCs with tolerated concentration profiles of teriflunomide led to a significant upregulation of CNPase, TAp73, Mash1/Ascl1, Myrf, Nkx2.2, PLP, and Sox 10 transcript levels	Short-term teriflunomide pulses can efficiently promote oligodendroglial cell differentiation suggesting that young, immature cells could benefit from such stimulation.	29534752	Details
Nkx2-2	Teriflunomide	activator	N/A	Wistar rat	Quantitative RT-PCR after 1d revealed that stimulation of primary rat OPCs with tolerated concentration profiles of teriflunomide led to a significant upregulation of CNPase, TAp73, Mash1/Ascl1, Myrf, Nkx2.2, PLP, and Sox 10 transcript levels	Short-term teriflunomide pulses can efficiently promote oligodendroglial cell differentiation suggesting that young, immature cells could benefit from such stimulation.	29534752	Details
Plp1	Teriflunomide	activator	N/A	Wistar rat	Quantitative RT-PCR after 1d revealed that stimulation of primary rat OPCs with tolerated concentration profiles of teriflunomide led to a significant upregulation of CNPase, TAp73, Mash1/Ascl1, Myrf, Nkx2.2, PLP, and Sox 10 transcript levels	Short-term teriflunomide pulses can efficiently promote oligodendroglial cell differentiation suggesting that young, immature cells could benefit from such stimulation.	29534752	Details
Sox10	Teriflunomide	activator	N/A	Wistar rat	Quantitative RT-PCR after 1d revealed that stimulation of primary rat OPCs with tolerated concentration profiles of teriflunomide led to a significant upregulation of CNPase, TAp73, Mash1/Ascl1, Myrf, Nkx2.2, PLP, and Sox 10 transcript levels	Short-term teriflunomide pulses can efficiently promote oligodendroglial cell differentiation suggesting that young, immature cells could benefit from such stimulation.	29534752	Details
FXN	Dimethyl fumarate	activator	MS	N/A	DMF dosed Multiple Sclerosis (MS) patients showed significant increase in FXN expression by ~85%	As a potential consequence, we observe significant reduction in both R-loop formation and transcriptional pausing thereby significantly increasing FXN expression	31158268	Details
Tnf	KW-2449	inhibitor	experimental autoimmune encephalomyelitis	C57BL/6	KW-2449 also decreased TNF-α, IL-6, CCL-2 inflammatory cytokines, and MMP-2 in both brain mRNA expressions and serum levels of EAE mice	The KW-2449, aging as a multi-kinase inhibitor, modulates the inflammatory responses of cytokine cascades either in the brain or in plasma	33155932	Details
Ccl2	KW-2449	inhibitor	experimental autoimmune encephalomyelitis	C57BL/6	KW-2449 also decreased TNF-α, IL-6, CCL-2 inflammatory cytokines, and MMP-2 in both brain mRNA expressions and serum levels of EAE mice	The KW-2449, aging as a multi-kinase inhibitor, modulates the inflammatory responses of cytokine cascades either in the brain or in plasma	33155932	Details
Il6	KW-2449	inhibitor	experimental autoimmune encephalomyelitis	C57BL/6	KW-2449 also decreased TNF-α, IL-6, CCL-2 inflammatory cytokines, and MMP-2 in both brain mRNA expressions and serum levels of EAE mice	The KW-2449, aging as a multi-kinase inhibitor, modulates the inflammatory responses of cytokine cascades either in the brain or in plasma	33155932	Details
Mmp2	KW-2449	inhibitor	experimental autoimmune encephalomyelitis	C57BL/6	KW-2449 also decreased TNF-α, IL-6, CCL-2 inflammatory cytokines, and MMP-2 in both brain mRNA expressions and serum levels of EAE mice	The KW-2449, aging as a multi-kinase inhibitor, modulates the inflammatory responses of cytokine cascades either in the brain or in plasma	33155932	Details
Sirt1	AAV2 vectors	activator	experimental autoimmune encephalomyelitis	C57BL/6	AAV2-SIRT1 mediated significant preservation of the OKR compared to AAV2-eGFP controls	AAV-mediated overexpression of NRF2 or SIRT1 within RGCs mediates distinct neuroprotective effects upon visual function and RGC survival	29494741	Details
Nfe2l2	AAV2 vectors	activator	experimental autoimmune encephalomyelitis	C57BL/6	Treatment with AAV2-NRF2 promoted RGC survival while AAV2-SIRT1 mediated an upward trend in protection compared to vehicle and AAV2-eGFP controls	AAV-mediated overexpression of NRF2 or SIRT1 within RGCs mediates distinct neuroprotective effects upon visual function and RGC survival	29494741	Details
Gata3	Gemfibrozil	activator	experimental autoimmune encephalomyelitis	C57BL/6	We demonstrated that treatment with gemfibrozil increases expression of the Th2 transcription factor GATA-3 and decreases expression of the Th1 transcription factor T-bet in vitro and directly ex vivo	Therefore, if PPARα, through interaction with its ligand, can regulate either of these transcription factors directly or indirectly, this could result in the regulation of the other transcription factor	19299749	Details
Tbx21	Gemfibrozil	inhibitor	experimental autoimmune encephalomyelitis	C57BL/6	We demonstrated that treatment with gemfibrozil increases expression of the Th2 transcription factor GATA-3 and decreases expression of the Th1 transcription factor T-bet in vitro and directly ex vivo	Therefore, if PPARα, through interaction with its ligand, can regulate either of these transcription factors directly or indirectly, this could result in the regulation of the other transcription factor.	19299749	Details
Il4	Gemfibrozil	activator	experimental autoimmune encephalomyelitis	C57BL/6	These data, in combination with the inability of gemfibrozil to increase IL-4 production when PPARα is silenced (Fig. 4), suggest that PPARα can transactivate the IL-4 promoter and that the binding is functional.	that PPARα can directly transactivate the IL-4 gene	19299749	Details
Esr2	LY3201	activator	experimental autoimmune encephalomyelitis	SJL/J mice	Treatment of EAE mice with LY3201, a selective ERβ agonist provided by Eli Lilly, resulted in marked reduction of activated microglia in the spinal cord	the ERβ-selective agonist LY3201 can inactivate microglia and invading T cells by down-regulating two important inflammatory pathways, NF-κB and iNOS	23401502	Details
Nog	GW0742	activator	experimental autoimmune encephalomyelitis	C57BL/6	noggin mRNA was only increased in astrocytes	We show that effects of GW0742 are mediated through PPARδ	20001953	Details
IL22	G2013	inhibitor	MS	N/A	the results show that G2013 is able to significantly reduce the gene expression of IL-22, AHR, RORC, and T-bet	he α-L-guluronic acid (G2013), is a novel immunosuppressive drug	32103523	Details
AHR	G2013	inhibitor	MS	N/A	the results show that G2013 is able to significantly reduce the gene expression of IL-22, AHR, RORC, and T-bet	he α-L-guluronic acid (G2013), is a novel immunosuppressive drug	32103523	Details
RORC	G2013	inhibitor	MS	N/A	the results show that G2013 is able to significantly reduce the gene expression of IL-22, AHR, RORC, and T-bet	he α-L-guluronic acid (G2013), is a novel immunosuppressive drug	32103523	Details
TBX21	G2013	inhibitor	MS	N/A	the results show that G2013 is able to significantly reduce the gene expression of IL-22, AHR, RORC, and T-bet	he α-L-guluronic acid (G2013), is a novel immunosuppressive drug	32103523	Details
CCL1	interferon beta	inhibitor	MS	N/A	CCL1, CCL2, CCL7, CXCL10, CXCL11, and CCR1 gene expression was strongly upregulated in interferon beta-treated	The peripheral upregulation of these chemokines may reduce the chemoattraction of immune cells to the central nervous system and thus add to the therapeutic effects of interferon beta	19667211	Details
CCL2	interferon beta	inhibitor	MS	N/A	CCL1, CCL2, CCL7, CXCL10, CXCL11, and CCR1 gene expression was strongly upregulated in interferon beta-treated	The peripheral upregulation of these chemokines may reduce the chemoattraction of immune cells to the central nervous system and thus add to the therapeutic effects of interferon beta	19667211	Details
CCL7	interferon beta	inhibitor	MS	N/A	CCL1, CCL2, CCL7, CXCL10, CXCL11, and CCR1 gene expression was strongly upregulated in interferon beta-treated	The peripheral upregulation of these chemokines may reduce the chemoattraction of immune cells to the central nervous system and thus add to the therapeutic effects of interferon beta	19667211	Details
CXCL10	interferon beta	inhibitor	MS	N/A	CCL1, CCL2, CCL7, CXCL10, CXCL11, and CCR1 gene expression was strongly upregulated in interferon beta-treated	The peripheral upregulation of these chemokines may reduce the chemoattraction of immune cells to the central nervous system and thus add to the therapeutic effects of interferon beta	19667211	Details
CXCL11	interferon beta	inhibitor	MS	N/A	CCL1, CCL2, CCL7, CXCL10, CXCL11, and CCR1 gene expression was strongly upregulated in interferon beta-treated	The peripheral upregulation of these chemokines may reduce the chemoattraction of immune cells to the central nervous system and thus add to the therapeutic effects of interferon beta	19667211	Details
CCR1	interferon beta	inhibitor	MS	N/A	CCL1, CCL2, CCL7, CXCL10, CXCL11, and CCR1 gene expression was strongly upregulated in interferon beta-treated	The peripheral upregulation of these chemokines may reduce the chemoattraction of immune cells to the central nervous system and thus add to the therapeutic effects of interferon beta	19667211	Details
Tnf	GW 501516	inhibitor	experimental autoimmune encephalomyelitis	N/A	GW 501516 decreased the IFN-gamma-induced up-regulation of TNF-alpha and iNOS in accord with the proposed anti-inflammatory effects of this PPAR-beta agonist	the protective effects of PPAR-beta agonists observed in vivo can be attributed to their anti-inflammatory properties rather than to a direct protective or trophic effect on oligodendrocytes	19422681	Details
Nos2	GW 501516	inhibitor	experimental autoimmune encephalomyelitis	N/A	GW 501516 decreased the IFN-gamma-induced up-regulation of TNF-alpha and iNOS in accord with the proposed anti-inflammatory effects of this PPAR-beta agonist	the protective effects of PPAR-beta agonists observed in vivo can be attributed to their anti-inflammatory properties rather than to a direct protective or trophic effect on oligodendrocytes	19422681	Details
Il6	GW 501516	activator	experimental autoimmune encephalomyelitis	N/A	it increased IL-6 m-RNA expression	the protective effects of PPAR-beta agonists observed in vivo can be attributed to their anti-inflammatory properties rather than to a direct protective or trophic effect on oligodendrocytes	19422681	Details
FOXP3	interferon (IFN)-β	activator	MS	N/A	We found that untreated MS patients had lower cell surface expression of cytotoxic T lymphocyte antigen 4 (CTLA-4) on CD4+CD25high T cells and higher intracellular CTLA-4 expression than healthy controls. Cell surface expression of CTLA-4 on CD4+CD25high T cells correlated with expression of FOXP3 mRNA in untreated patients and increased significantly with time from most recent injection in patients treated with IFN-β	Expression of the forkhead box protein 3 (FoxP3) transcription factor is regulated by the E3 ubiquitin ligases Itch and Cbl-b and induces regulatory activity CD4+CD25high T cells	23039885	Details
IL1B	Simvastatin	inhibitor	MS	RRMS	We report that simvastatin inhibits IL-1β, IL-23, TGF-β, IL-21, IL-12p70, and induces IL-27 secretion from DCs in RRMS patients, providing an inhibitory cytokine milieu for Th17 and Th1-cell differentiation	widely used cholesterol-lowering agents, have also been demonstrated to have antiinflammatory effects	23076801	Details
IL23A	Simvastatin	inhibitor	MS	RRMS	We report that simvastatin inhibits IL-1β, IL-23, TGF-β, IL-21, IL-12p70, and induces IL-27 secretion from DCs in RRMS patients, providing an inhibitory cytokine milieu for Th17 and Th1-cell differentiation	widely used cholesterol-lowering agents, have also been demonstrated to have antiinflammatory effects	23076801	Details
TGFB1	Simvastatin	inhibitor	MS	RRMS	We report that simvastatin inhibits IL-1β, IL-23, TGF-β, IL-21, IL-12p70, and induces IL-27 secretion from DCs in RRMS patients, providing an inhibitory cytokine milieu for Th17 and Th1-cell differentiation	widely used cholesterol-lowering agents, have also been demonstrated to have antiinflammatory effects	23076801	Details
IL21	Simvastatin	inhibitor	MS	RRMS	We report that simvastatin inhibits IL-1β, IL-23, TGF-β, IL-21, IL-12p70, and induces IL-27 secretion from DCs in RRMS patients, providing an inhibitory cytokine milieu for Th17 and Th1-cell differentiation	widely used cholesterol-lowering agents, have also been demonstrated to have antiinflammatory effects	23076801	Details
IL12A	Simvastatin	inhibitor	MS	RRMS	We report that simvastatin inhibits IL-1β, IL-23, TGF-β, IL-21, IL-12p70, and induces IL-27 secretion from DCs in RRMS patients, providing an inhibitory cytokine milieu for Th17 and Th1-cell differentiation	widely used cholesterol-lowering agents, have also been demonstrated to have antiinflammatory effects	23076801	Details
IL27	Simvastatin	activator	MS	RRMS	We report that simvastatin inhibits IL-1β, IL-23, TGF-β, IL-21, IL-12p70, and induces IL-27 secretion from DCs in RRMS patients, providing an inhibitory cytokine milieu for Th17 and Th1-cell differentiation	widely used cholesterol-lowering agents, have also been demonstrated to have antiinflammatory effects	23076801	Details
Il10	GSK3	activator	experimental autoimmune encephalomyelitis	B10.PL (H2u) mice	treatment of Th1 and Th2 cells with GSK3 inhibitors dramatically increased production of IL-10	The serine/threonine kinase glycogen synthase kinase-3 (GSK3) plays an important role in balancing pro- and anti-inflammatory cytokine	25627813	Details
IL10	GSK3	activator	MS	N/A	GSK3 inhibition also led to upregulation of IL-10 among Th1, Th2, and Th17 subsets isolated from human blood	The serine/threonine kinase glycogen synthase kinase-3 (GSK3) plays an important role in balancing pro- and anti-inflammatory cytokine	25627813	Details
NQO1	DMF	activator	MS	N/A	In DMF-treated patients, a statistically significant induction of NQO1 was observed relative to baseline and compared to placebo	DMF activated the nuclear factor E2-related factor 2 (Nrf2) pathway	28156185	Details
HMOX1	DMF	N/A	MS	N/A	No statistical significance was reached for HO1 induction	DMF activated the nuclear factor E2-related factor 2 (Nrf2) pathway	28156185	Details
SOCS3	Simvastatin	activator	MS	RRMS	Our results demonstrated statin-mediated increases in suppressor of cytokine secretion (SOCS) 3 and suppressor of cytokine secretion 7, which negatively regulate the STAT/JAK signal transduction pathway and IL-6 and IL-23 gene expression in monocytes	These results provide evidence for the novel immunomodulatory mechanisms of statins, which selectively target the regulation of cytokine transcription involved in the development of the human autoimmune response	18453621	Details
SOCS7	Simvastatin	activator	MS	RRMS	Our results demonstrated statin-mediated increases in suppressor of cytokine secretion (SOCS) 3 and suppressor of cytokine secretion 7, which negatively regulate the STAT/JAK signal transduction pathway and IL-6 and IL-23 gene expression in monocytes	These results provide evidence for the novel immunomodulatory mechanisms of statins, which selectively target the regulation of cytokine transcription involved in the development of the human autoimmune response	18453621	Details
IL6	Simvastatin	inhibitor	MS	RRMS	Our results demonstrated statin-mediated increases in suppressor of cytokine secretion (SOCS) 3 and suppressor of cytokine secretion 7, which negatively regulate the STAT/JAK signal transduction pathway and IL-6 and IL-23 gene expression in monocytes	These results provide evidence for the novel immunomodulatory mechanisms of statins, which selectively target the regulation of cytokine transcription involved in the development of the human autoimmune response	18453621	Details
IL23A	Simvastatin	inhibitor	MS	RRMS	Our results demonstrated statin-mediated increases in suppressor of cytokine secretion (SOCS) 3 and suppressor of cytokine secretion 7, which negatively regulate the STAT/JAK signal transduction pathway and IL-6 and IL-23 gene expression in monocytes	These results provide evidence for the novel immunomodulatory mechanisms of statins, which selectively target the regulation of cytokine transcription involved in the development of the human autoimmune response	18453621	Details
IFNG	Simvastatin	activator	MS	RRMS	Simvastatin also induced IFN-gamma, IL-4, and IL-27 production in monocytes, which together inhibited IL-17 transcription and secretion in CD4(+) T cells	These results provide evidence for the novel immunomodulatory mechanisms of statins, which selectively target the regulation of cytokine transcription involved in the development of the human autoimmune response	18453621	Details
IL4	Simvastatin	activator	MS	RRMS	Simvastatin also induced IFN-gamma, IL-4, and IL-27 production in monocytes, which together inhibited IL-17 transcription and secretion in CD4(+) T cells	These results provide evidence for the novel immunomodulatory mechanisms of statins, which selectively target the regulation of cytokine transcription involved in the development of the human autoimmune response	18453621	Details
IL27	Simvastatin	activator	MS	RRMS	Simvastatin also induced IFN-gamma, IL-4, and IL-27 production in monocytes, which together inhibited IL-17 transcription and secretion in CD4(+) T cells	These results provide evidence for the novel immunomodulatory mechanisms of statins, which selectively target the regulation of cytokine transcription involved in the development of the human autoimmune response	18453621	Details
IFNG	vitamin A	inhibitor	MS	N/A	The results showed that after 6 months of supplementation, expression of IFN-γ and T-bet was significantly decreased	These results provide evidence for the novel immunomodulatory mechanisms of statins, which selectively target the regulation of cytokine transcription involved in the development of the human autoimmune response	27122150	Details
TBX21	vitamin A	inhibitor	MS	N/A	The results showed that after 6 months of supplementation, expression of IFN-γ and T-bet was significantly decreased	These results provide evidence for the novel immunomodulatory mechanisms of statins, which selectively target the regulation of cytokine transcription involved in the development of the human autoimmune response	27122150	Details
MIRLET7C	Natalizumab	inhibitor	MS	N/A	We found that the expression level of three miRNAs (let-7c, miR-125a-5p and miR-642) was affected after 6 months of therapy	Natalizumab has shown its efficacy in reducing multiple sclerosis (MS) relapses and progression of disability	24852919	Details
MIR125A	Natalizumab	inhibitor	MS	N/A	We found that the expression level of three miRNAs (let-7c, miR-125a-5p and miR-642) was affected after 6 months of therapy	Natalizumab has shown its efficacy in reducing multiple sclerosis (MS) relapses and progression of disability	24852919	Details
MIR642A	Natalizumab	activator	MS	N/A	We found that the expression level of three miRNAs (let-7c, miR-125a-5p and miR-642) was affected after 6 months of therapy	Natalizumab has shown its efficacy in reducing multiple sclerosis (MS) relapses and progression of disability	24852919	Details
MIR320A	Natalizumab	activator	MS	N/A	We found that the expression level of three miRNAs (let-7c, miR-125a-5p and miR-642) was affected after 6 months of therapy	Natalizumab has shown its efficacy in reducing multiple sclerosis (MS) relapses and progression of disability	24852919	Details
MIR320B1	Natalizumab	activator	MS	N/A	We found that the expression level of three miRNAs (let-7c, miR-125a-5p and miR-642) was affected after 6 months of therapy	Natalizumab has shown its efficacy in reducing multiple sclerosis (MS) relapses and progression of disability	24852919	Details
MIR629	Natalizumab	inhibitor	MS	N/A	We found that the expression level of three miRNAs (let-7c, miR-125a-5p and miR-642) was affected after 6 months of therapy	Natalizumab has shown its efficacy in reducing multiple sclerosis (MS) relapses and progression of disability	24852919	Details
Tnf	BMSC-BDNF	inhibitor	experimental autoimmune encephalomyelitis	SJL/J female mice	Inhibition of pro-inflammatory cytokines TNF-alpha and IFN-gamma and enhanced expression of the antiinflammatory cytokines IL-4, IL-10, and IL-11 were found in the CNS tissues of the BDNF transplanted group.	BDNF is neuroprotective in animal models of neurodegenerative diseases.In addition, pathological examination showed that BDNF delivery reduced demyelination and increased remyelination	19361871	Details
Ifng	BMSC-BDNF	inhibitor	experimental autoimmune encephalomyelitis	SJL/J female mice	Inhibition of pro-inflammatory cytokines TNF-alpha and IFN-gamma and enhanced expression of the antiinflammatory cytokines IL-4, IL-10, and IL-11 were found in the CNS tissues of the BDNF transplanted group.	BDNF is neuroprotective in animal models of neurodegenerative diseases.In addition, pathological examination showed that BDNF delivery reduced demyelination and increased remyelination	19361871	Details
Il4	BMSC-BDNF	activator	experimental autoimmune encephalomyelitis	SJL/J female mice	Inhibition of pro-inflammatory cytokines TNF-alpha and IFN-gamma and enhanced expression of the antiinflammatory cytokines IL-4, IL-10, and IL-11 were found in the CNS tissues of the BDNF transplanted group.	BDNF is neuroprotective in animal models of neurodegenerative diseases.In addition, pathological examination showed that BDNF delivery reduced demyelination and increased remyelination	19361871	Details
Il10	BMSC-BDNF	activator	experimental autoimmune encephalomyelitis	SJL/J female mice	Inhibition of pro-inflammatory cytokines TNF-alpha and IFN-gamma and enhanced expression of the antiinflammatory cytokines IL-4, IL-10, and IL-11 were found in the CNS tissues of the BDNF transplanted group.	BDNF is neuroprotective in animal models of neurodegenerative diseases.In addition, pathological examination showed that BDNF delivery reduced demyelination and increased remyelination	19361871	Details
Il11	BMSC-BDNF	activator	experimental autoimmune encephalomyelitis	SJL/J female mice	Inhibition of pro-inflammatory cytokines TNF-alpha and IFN-gamma and enhanced expression of the antiinflammatory cytokines IL-4, IL-10, and IL-11 were found in the CNS tissues of the BDNF transplanted group.	BDNF is neuroprotective in animal models of neurodegenerative diseases.In addition, pathological examination showed that BDNF delivery reduced demyelination and increased remyelination	19361871	Details
Lingo1	LV/Lingo-1-shRNA	inhibitor	experimental autoimmune encephalomyelitis	C57BL/6	The data showed that administering LV/Lingo-1-shRNA by ICV injection could efficiently knockdown Lingo-1 expression in vivo	improve functional recovery and enhance myelination/remyelination	25045138	Details
Ifng	IL-12 p40	inhibitor	experimental autoimmune encephalomyelitis	PL/J mice、B10.PL mice	High levels of IL-12 p40 expression reduces IFN-_x005fproductionin transduced MBP-specific T cells；IL-12 p40 inhibits IFN-production in developing and effectorCD4βT cell populations	These data suggest that IL-12 p40can act therapeutically by interrupting Th1-mediated inflammatoryautoimmune responses	11490028	Details
IFNAR1	IFN-β	inhibitor	MS	N/A	There was a significant decrease of IFNAR1 and IFNAR2 mRNA expression and a significant increase of CCR5 mRNA expression in MS patients compared with the control group	It exerts its effect by reducing T-cell activation, inhibiting IFN-γ effects and the blood–brain barrier leakage, and inducing an immune deviation, either by inhibiting T helper-1 (Th-1) or by promoting T helper-2 (Th-2) cytokines production	27346865	Details
IFNAR2	IFN-β	inhibitor	MS	N/A	There was a significant decrease of IFNAR1 and IFNAR2 mRNA expression and a significant increase of CCR5 mRNA expression in MS patients compared with the control group	N/A	27346865	Details
CCR5	IFN-β	activator	MS	N/A	There was a significant decrease of IFNAR1 and IFNAR2 mRNA expression and a significant increase of CCR5 mRNA expression in MS patients compared with the control group	N/A	27346865	Details
H2	inactivated influenza vaccine	N/A	experimental autoimmune encephalomyelitis	C57BL/6	The results obtained show that influenza vaccine has no significant influence on EAE induction and severity of autoimmune processes	N/A	23865440	Details
Il4	Ad-IL4-MSCs	activator	experimental autoimmune encephalomyelitis	C57BL/6	Notably, the early administration of Ad-IL4-MSCs in mice with EAE at the time of T-cell priming attenuated clinical disease	This protective effect was associated with a reduction in peripheral MOG-specific T-cell responses and a shift from a pro- to an anti-inflammatory cytokine response	22568986	Details
Ahr	Laquinimod	activator	experimental autoimmune encephalomyelitis	C57BL/6	Laq Ameliorates Autoimmune CNS Inflammation Independent of AHR in Myeloid Cells	Laq administration led to the activation of AHR in astrocytes, which was associated with clinical improvement during late stages of EAE, reduction of CNS-infiltrating proinflammatory monocytes and T-cell numbers, and polarization	33408169	Details
Mmp9	Rolipram	inhibitor	experimental autoimmune encephalomyelitis	Lewis rats	Rolipram reduces the MMP-9 gene expression in LNCsand CNS from EAE animals	The available evidence points towards NF-nB inhibition as one of the key therapeutic mechanisms whichwould mediate down-regulation of genes codifying for proteins involved in cell migration	16182379	Details
Hmox1	Snpp-9	inhibitor	experimental autoimmune encephalomyelitis	Wistar rats	After a specific inhibitor of HO-1, Snpp-9, was applied, both of the symptoms and pathological lesions of EAE in the rat brains were mitigated markedly	Antioxidant effect	15497037	Details
HBD	fingolimod	inhibitor	MS	N/A	immunomodulatory therapies with fingolimod, DMF, and IFNβ-1α have significantly decreased HBD expression	immunomodulatory therapies	34504491	Details
HBD	DMF	inhibitor	MS	N/A	immunomodulatory therapies with fingolimod, DMF, and IFNβ-1α have significantly decreased HBD expression	immunomodulatory therapies	34504491	Details
HBD	IFNβ-1α	inhibitor	MS	N/A	immunomodulatory therapies with fingolimod, DMF, and IFNβ-1α have significantly decreased HBD expression	immunomodulatory therapies	34504491	Details
Tnf	Piperine	inhibitor	experimental autoimmune encephalomyelitis	female Lewis rats	Gene expression analysis in lumbar spinal cord showed that piperine treatment decreased the level of pro-inflammatory cytokines (TNF-α, IL-1β) and iNOS and enhanced IL-10, Nrf2, HO-1, and MBP expressions	the efficiency of piperine on progression of EAE model and myelin repair mechanisms was investigated	34338970	Details
Il1b	Piperine	inhibitor	experimental autoimmune encephalomyelitis	female Lewis rats	Gene expression analysis in lumbar spinal cord showed that piperine treatment decreased the level of pro-inflammatory cytokines (TNF-α, IL-1β) and iNOS and enhanced IL-10, Nrf2, HO-1, and MBP expressions	the efficiency of piperine on progression of EAE model and myelin repair mechanisms was investigated	34338970	Details
Il10	Piperine	activator	experimental autoimmune encephalomyelitis	female Lewis rats	Gene expression analysis in lumbar spinal cord showed that piperine treatment decreased the level of pro-inflammatory cytokines (TNF-α, IL-1β) and iNOS and enhanced IL-10, Nrf2, HO-1, and MBP expressions	the efficiency of piperine on progression of EAE model and myelin repair mechanisms was investigated	34338970	Details
Nfe2l2	Piperine	activator	experimental autoimmune encephalomyelitis	female Lewis rats	Gene expression analysis in lumbar spinal cord showed that piperine treatment decreased the level of pro-inflammatory cytokines (TNF-α, IL-1β) and iNOS and enhanced IL-10, Nrf2, HO-1, and MBP expressions	the efficiency of piperine on progression of EAE model and myelin repair mechanisms was investigated	34338970	Details
Hmox1	Piperine	activator	experimental autoimmune encephalomyelitis	female Lewis rats	Gene expression analysis in lumbar spinal cord showed that piperine treatment decreased the level of pro-inflammatory cytokines (TNF-α, IL-1β) and iNOS and enhanced IL-10, Nrf2, HO-1, and MBP expressions	the efficiency of piperine on progression of EAE model and myelin repair mechanisms was investigated	34338970	Details
Mbp	Piperine	activator	experimental autoimmune encephalomyelitis	female Lewis rats	Gene expression analysis in lumbar spinal cord showed that piperine treatment decreased the level of pro-inflammatory cytokines (TNF-α, IL-1β) and iNOS and enhanced IL-10, Nrf2, HO-1, and MBP expressions	the efficiency of piperine on progression of EAE model and myelin repair mechanisms was investigated	34338970	Details
TLR2	G2013	inhibitor	MS	N/A	Our research indicated that this drug could significantly decrease the gene expression of TLR2, TLR4 and TNF-α compared to untreated group	reducing the pathological process	31594427	Details
TLR4	G2013	inhibitor	MS	N/A	Our research indicated that this drug could significantly decrease the gene expression of TLR2, TLR4 and TNF-α compared to untreated group	reducing the pathological process	31594427	Details
TNFAIP3	G2013	inhibitor	MS	N/A	Our research indicated that this drug could significantly decrease the gene expression of TLR2, TLR4 and TNF-α compared to untreated group	reducing the pathological process	31594427	Details
HLA-DRB1	Cop-1	activator	MS	N/A	Data have shown a possible positive correlation between presence of DRB1*1501 and response to Cop-1 therapy	Copolymer 1 (Cop-1) is a random synthetic amino acid copolymer, effective in the treatment of the relapsing-remitting form of MS	11739812	Details
TSC22D3	IVMP	activator	MS	N/A	GILZ and MCL-1 gene expression were significantly higher following first IVMP treatment in responders, compared to non-responders	Glucocorticoids (GCs) are the main treatment of relapse in multiple sclerosis (MS)	34593869	Details
MCL1	IVMP	activator	MS	N/A	GILZ and MCL-1 gene expression were significantly higher following first IVMP treatment in responders, compared to non-responders	Glucocorticoids (GCs) are the main treatment of relapse in multiple sclerosis (MS)	34593869	Details
GSTP1	Natalizumab	activator	MS	N/A	Among our cohort of MS patients, 88.5% responded and 11.5% manifested clinical deterioration after natalizumab treatment	oxidative stress reduction might be another mechanism through which natalizumab exerts its protective effect	27993870	Details
NQO1	Natalizumab	activator	MS	N/A	Among our cohort of MS patients, 88.5% responded and 11.5% manifested clinical deterioration after natalizumab treatment	oxidative stress reduction might be another mechanism through which natalizumab exerts its protective effect	27993870	Details
Il10	XT-101-R	activator	experimental autoimmune encephalomyelitis	Male Dark Agouti rats	XT-101-R reversed motor symptoms, and attenuated loss of body weight, the standard outcome measures for EAE.	IL-10 has the potential to decrease disease severity by decreasing expression of pro-inflammatory cytokines, decreasing antigen presentation, inducing T cell anergy and promoting neuroprotection	27189037	Details
Il17a	Carvacrol	inhibitor	experimental autoimmune encephalomyelitis	Lewis rats	Carvacrol administration reversed the mRNA IL-1 and NF-κB to below the control group level	carvacrol effectively suppresses immune and inflammatory processes	36580874	Details
Rela	Carvacrol	inhibitor	experimental autoimmune encephalomyelitis	Lewis rats	Carvacrol administration reversed the mRNA IL-1 and NF-κB to below the control group level	carvacrol effectively suppresses immune and inflammatory processes	36580874	Details
Tnf	Carvacrol	N/A	experimental autoimmune encephalomyelitis	Lewis rats	Carvacrol administration did not significantly affect the TNF-α level of gene expression	N/A	36580874	Details
Mbp	Carvacrol	activator	experimental autoimmune encephalomyelitis	Lewis rats	Carvacrol administration significantly reduced the expression of IL-1, IL-17, and NF-κB and increased MBP and OLIG2 expression	MBP production increased indicating the trend of myelination.	36580874	Details
Olig2	Carvacrol	activator	experimental autoimmune encephalomyelitis	Lewis rats	Carvacrol administration significantly reduced the expression of IL-1, IL-17, and NF-κB and increased MBP and OLIG2 expression	Increased OLIG2 expression also increases the production of differentiated oligodendrocytes and leads to premature CNS myelination	36580874	Details
Pdgfra	Carvacrol	N/A	experimental autoimmune encephalomyelitis	Lewis rats	we found no significant difference between the carvacrol-treated and the control groups.	N/A	36580874	Details
Il10	pVAXhsp65	activator	experimental autoimmune encephalomyelitis	C57BL/6	Previous immunization with pVAXhsp65 significantly reduced EAE symptoms. Infiltrating cells from the CNS stimulated with rhsp65 produced significantly higher levels of IL-10.	IL-10 producer cells, specific for MOG35–55 or hsp65, had migrated to the CNS and partially controlled inflammation.	28321419	Details
Nfe2l2	spinal cord	N/A	experimental autoimmune encephalomyelitis	C57BL/6	In mice deficient for nuclear factor (erythroid-derived 2)-related factor 2 on the same genetic background, the dimethylfumarate mediated beneficial effects on clinical course, axon preservation and astrocyte activation were almost completely abolished thus proving the functional relevance of this transcription factor for the neuroprotective mechanism of action.	where dimethylfumarate applicationmay lead to direct Nrf2 activation, not only in different neuronalpopulations, but also in oligodendrocytes and astrocytes	21354971	Details
S1pr1	Ponesimod	activator	experimental autoimmune encephalomyelitis	C57Bl/6J	These data support the CNS activities of ponesimod through S1P1 , including protective, and likely selective, effects against demyelination in a major connection pathway of the brain, the limbic fibers of the cingulum, lesions of which have been associated with several neurologic impairments including MS fatigue.	Ponesimod is a sphingosine 1-phosphate (S1P) receptor (S1PR) modulator that was recently approved for treating relapsing forms of multiple sclerosis (MS).	34986275	Details
RORC	EGCG	inhibitor	MS	NA	However, EGCG did not influence the level of HIF-1α. Our present data has led us to conclude that EGCG could be considered as an anti-inflammatory agent may serve as an achievable therapeutic agent for MS.	Multiple Sclerosis (MS) is the chronic inflammation of the Central Nervous System (CNS) and autoimmune disease.	35154593	Details
Il17a	CpdA	inhibitor	experimental autoimmune encephalomyelitis	C57BL/6J	Administration of high-dose CpdA to mice was lethal while treatment of EAE with low to intermediate amounts of CpdA dissolved in water significantly ameliorated the disease	The beneficial effect of CpdA required expression of the GR in T cells and was achieved by down regulating LFA-1 and CD44 on peripheral Th cells and by repressing IL-17 production.	19997594	Details
Il4	the IL-4 gene-containing vector	inhibitor	experimental autoimmune encephalomyelitis	Biozzi AB/H	Our results, showing that IL-4 gene delivery using HSV-1 vectors induces protection from EAE by in situ modulating the cytokine/chemokine-mediated circuits sustaining effector cell functions, indicate that the intrathecal 'therapeutic' use of nonreplicative HSV-1-derived vectors containing anti-inflammatory molecules might represent an alternative strategy in inflammatory diseases of the CNS.	Our results, showing that IL-4 gene delivery using HSV-1 vectors induces protection from EAE by in situ modulating the cytokine/chemokine-mediated circuits sustaining effector cell functions, indicate that the intrathecal 'therapeutic' use of nonreplicative HSV-1-derived vectors containing anti-inflammatory molecules might represent an alternative strategy in inflammatory diseases of the CNS.	11402297	Details
Il17a	dimethyl fumarate (DMF)	N/A	experimental autoimmune encephalomyelitis	C57BL/6J	herapeutic DMF application significantly reduced EAE severity, reflected by reduced T cell and CD8 T cell numbers, as well as by decreased frequency of Tc17 cells in the CNS	ence, DMF treatment caused a loss of the Tc17-dependent Th17 pathogenicity and conferred a stable “low IL-17” phenotype to Tc17 cells, suggesting a mechanism for amelioration of autoimmunity in CNS upon DMF treatment.	31844089	Details
Mir132	2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)	activator	experimental autoimmune encephalomyelitis	C57Bl/6J	Here, we show that TCDD induces cholinergic anti-inflammation in EAE mice by upregulating acetylcholinesterase-targeting miR-132. The expression of miR-132 was downregulated in CD4 cells and associated with EAE severity, while TCDD treatment attenuated EAE by inducing the miR-132/acetylcholinesterase module	Here, we show that TCDD induces cholinergic anti-inflammation in EAE mice by upregulating acetylcholinesterase-targeting miR-132. The expression of miR-132 was downregulated in CD4 cells and associated with EAE severity, while TCDD treatment attenuated EAE by inducing the miR-132/acetylcholinesterase module	23780851	Details
Bhlhe40	Nimodipine	activator	experimental autoimmune encephalomyelitis	Oli-Neu	Increased expression	This growth factor increases the production of cytokines in T cells. The factor itself is regulated by the vitamin D receptor.	36835129	Details
Nr4a1	Nimodipine	activator	experimental autoimmune encephalomyelitis	Oli-Neu	Increased expression	NR41A is expressed in several cell types. Nr41a is known to prevent immune cell infiltration into the CNS.	36835129	Details
Mt1	Nimodipine	activator	experimental autoimmune encephalomyelitis	Oli-Neu	Increased expression	MT1 is capable of binding to free radicals and heavy metal ions and has neuroprotective potential in the CNS; Mt1/ and Mt2/ EAE mice display an increased number of CNS lesions.	36835129	Details
Cyb5r1	Nimodipine	activator	experimental autoimmune encephalomyelitis	Oli-Neu	Increased expression	CYB5R1 expression has been described to increase the brain volume in the early phases of development.	36835129	Details
Nr1d1	Nimodipine	activator	experimental autoimmune encephalomyelitis	Oli-Neu	Increased expression	This nuclear receptor displays higher expression in neuronal stem cells than fetal cells.	36835129	Details
Gap43	Nimodipine	inhibitor	experimental autoimmune encephalomyelitis	Oli-Neu	Decreased expression	The level of GAP43 correlates negatively with the formation of myelin in gray matter.	36835129	Details
Ddit3	Nimodipine	activator	experimental autoimmune encephalomyelitis	Oli-Neu	Increased expression	DDIT3 is activated when demyelination occurs. In the cuprizone mouse model, Ddit3-/- knockout mice show reduced demyelination.	36835129	Details
Sesn2	Nimodipine	activator	experimental autoimmune encephalomyelitis	Oli-Neu	Increased expression	SESN2 has been described as a universal growth factor. In MS patients, serum levels of SESN2 are decreased.	36835129	Details
Gadd45b	Nimodipine	activator	experimental autoimmune encephalomyelitis	Oli-Neu	Increased expression	The DNA methylase, GADD45B, increases transcription and stimulates axonal regeneration	36835129	Details
Serpini1	Nimodipine	inhibitor	experimental autoimmune encephalomyelitis	Oli-Neu	Decreased expression	The direct effect of SERPINI1 is unknown. It is speculated that there is a negative correlation between neuronal growth and SERPINI1 expression.	36835129	Details
Pik3r3	Nimodipine	activator	experimental autoimmune encephalomyelitis	Oli-Neu	Increased expression	PIK3R3 regulates lipid metabolism and is part of a myelin synthesis pathway.	36835129	Details
Cntfr	Nimodipine	activator	experimental autoimmune encephalomyelitis	Oli-Neu	Increased expression	CNTFR controls the expression of MOG	36835129	Details
Magi2	Nimodipine	activator	experimental autoimmune encephalomyelitis	Oli-Neu	Increased expression	MAGI2 has been described to be involved in synaptic transmission. MAGI2 expression was decreased in EAE.	36835129	Details
S100A2	Nimodipine	activator	experimental autoimmune encephalomyelitis	Oli-Neu	Increased expression	This calcium sensor is crucial for the organization of the cytoskeleton and the microtubule network in oligodendrocytes.	36835129	Details
Oxsr1	Nimodipine	activator	experimental autoimmune encephalomyelitis	Oli-Neu	Increased expression	OXSR1 is upregulated when embryonic stem cells change to OPCs.	36835129	Details
Tsc22d1	Nimodipine	activator	experimental autoimmune encephalomyelitis	Oli-Neu	Increased expression	TSC22D1 is a transcription factor that is upregulated in oligodendrocytes and downregulated in astrocytes	36835129	Details
Cdk1	Nimodipine	activator	experimental autoimmune encephalomyelitis	Oli-Neu	Increased expression	CDC2, which regulates the cell cycle, is present in OPCs but absent in mature oligodendrocytes	36835129	Details
Pfdn5	Nimodipine	inhibitor	experimental autoimmune encephalomyelitis	Oli-Neu	Decreased expression	PFDN5 is a molecular chaperone that stabilizes newly-synthesized proteins, allowing them to fold correctly. It is decreased in aging OPCs	36835129	Details
Mknk	Nimodipine	activator	experimental autoimmune encephalomyelitis	Oli-Neu	Increased expression	This kinase is responsible for lipid synthesis in oligodendrocytes.	36835129	Details
Mir106a	Nimodipine	activator	experimental autoimmune encephalomyelitis	Oli-Neu	Lower expression in blood samples and in gray matter lesions of MS patients	miR-106 is a negative regulator for the amyloid precursor protein	36835129	Details
Mir219a-2	Nimodipine	activator	experimental autoimmune encephalomyelitis	Oli-Neu	Lower expression in the cerebrospinal fluid of MS patients and in gray matter lesions	miR-219 is crucial for developing OPCs via, e.g., the suppression of caspase 3 expression	36835129	Details
Mir219b	Nimodipine	activator	experimental autoimmune encephalomyelitis	Oli-Neu	Lower expression in the cerebrospinal fluid of MS patients and in gray matter lesions	miR-219 is crucial for developing OPCs via, e.g., the suppression of caspase 3 expression	36835129	Details
Mir20a	Nimodipine	inhibitor	experimental autoimmune encephalomyelitis	Oli-Neu	Lower expression in gray matter lesions in MS patients	miR-20a suppresses the expression of NF-κB and IL-17/IL-23	36835129	Details
Mir34a	Nimodipine	activator	experimental autoimmune encephalomyelitis	Oli-Neu	Decreased expression	miR-34a-3p acts as a target for CD47. CD47 is a “do not eat me” surface marker	36835129	Details
Mir23a	Nimodipine	activator	experimental autoimmune encephalomyelitis	Oli-Neu	Expression is reduced in gray matter lesions in MS patients	miR-23 is a negative regulator of lamin B1, which is essential for oligodendrogenesis	36835129	Details
Mir338	Nimodipine	activator	experimental autoimmune encephalomyelitis	Oli-Neu	Decreased expression in white and gray matter lesions of MS patients	Interaction partner of miR-219; increases the expression of myelin	36835129	Details
Mir7-1	Nimodipine	activator	experimental autoimmune encephalomyelitis	Oli-Neu	Downregulation in white matter lesions of MS patients	miR-7 inhibits Wnt and activates Shh signaling, both of which increase myelination	36835129	Details
Mir122	Nimodipine	inhibitor	experimental autoimmune encephalomyelitis	Oli-Neu	Expression is increased in white matter lesions of MS patients	miR-122 expression increases the expression of proinflammatory type I interferons	36835129	Details
Tgfb1	sodium benzoate (NaB)	activator	experimental autoimmune encephalomyelitis	PLP139–151-specific 5B6 TCR Tg mice	These studies identify a new function of NaB in upregulating TGFβ via activation of STAT6, which may be beneficial in MS patients.	Here, we demonstrated that NaB induced the expression of TGFβ mRNA and protein in normal as well as proteolipid protein-primed splenocytes. Presence of a consensus STAT6-binding site in the promoter of TGFβ gene, activation of STAT6 in splenocytes by NaB, recruitment of STAT6 to the TGFβ promoter by NaB, and abrogation of NaB-induced expression of TGFβ in splenocytes by siRNA knockdown of STAT6 suggest that NaB induces the expression of TGFβ via activation of STAT6.	27605008	Details
Itga4	antisense oligonucleotides(ASO)	inhibitor	experimental autoimmune encephalomyelitis	C57Bl/6J	With the promising results in ameliorating disease progression, we are optimistic that the candidate oligomer may also be applicable to many other diseases associated with integrin alpha 4 mediated inflammation.	This highly specific strategy to down-regulate protein expression through interfering with normal exon selection during pre-mRNA processing should be applicable to many other gene targets that undergo splicing during expression	31506448	Details
Vegf	Adenoviral delivery of soluble VEGF receptor 1 (sFlt-1)	inhibitor	experimental autoimmune encephalomyelitis	C57Bl/6J	This study demonstrates that sFlt-1(1-3) gene transfer into the brain ameliorates the severity of EAE by inhibiting monocyte recruitment in the CNS of dark Agouti rats.	Previous studies have shown that vascular endothelial growth factor (VEGF) expression is up-regulated in both multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), a model for MS, and may exacerbate the disease.	18721816	Details
CXCL10	a combination of both phytocannabinoids (1:1 ratio, 10:10 μM)	inhibitor	MS	NA	THC and CBD (delivered in 1:1 combination at 10 μM) attenuated TLR3-induced CXCL10 and IFN-β protein expression in PBMCs from pwMS and HCs, and this effect was not seen consistently when THC and CBD were delivered alone.	The innate immune response to bacterial and viral molecules involves the coordinated production of cytokines, chemokines, and type I interferons (IFNs), which is orchestrated by toll-like receptors (TLRs)	35335126	Details
IFNB1	a combination of both phytocannabinoids (1:1 ratio, 10:10 μM)	inhibitor	MS	NA	THC and CBD (delivered in 1:1 combination at 10 μM) attenuated TLR3-induced CXCL10 and IFN-β protein expression in PBMCs from pwMS and HCs, and this effect was not seen consistently when THC and CBD were delivered alone.	The innate immune response to bacterial and viral molecules involves the coordinated production of cytokines, chemokines, and type I interferons (IFNs), which is orchestrated by toll-like receptors (TLRs)	35335126	Details
TNF	a combination of both phytocannabinoids (1:1 ratio, 10:10 μM)	activator	MS	NA	In terms of LPS, TLR4 activation promoted TNF-α expression in PBMCs from both cohorts, and, interestingly , CBD when delivered alone at 10 μM, and in combination with THC (in 1:1 combination at 10 μM), exacerbated TLR4-induced TNF-α protein expression in PBMCs from pwMS and HCs.	The aim of this study was to assess the impact of THC and CBD, when delivered in isolation and in combination (1:1), on TLR3- and TLR4-dependent signalling in peripheral blood mononuclear cells (PBMCs) from people with MS (pwMS; n = 21) and healthy controls (HCs; n = 26).	35335126	Details
CXCR4	IFN-β	inhibitor	RRMS	NA	Circulating MSCs, IP-10 and SDF-1α levels, increased in RRMS patients with clinically active not on DMT and IFN-β therapy reduced circulating MSCs and SDF-1α levels.	Mesenchymal stem cells (MSCs) have the capacity to migrate into the inflammatory regions in response to chemokines such as, IP-10 and SDF-1α and function as anti-inflammatory and immunomodulatory cells	31421626	Details
CAMP	F1-12h	activator	MS	NA	In summary, our data demonstrate that the two novel FTY720 derivatives act as anti-inflammatory ultimately by influencing the gene expression via the cAMP and downstream transcription factor CRE pathway	Fingolimod (FTY720) is an orally active immunomodulatory drug that has been used for the treatment of relapsing-remitting multiple sclerosis.	27913115	Details
CAMP	F2-9	activator	MS	NA	In summary, our data demonstrate that the two novel FTY720 derivatives act as anti-inflammatory ultimately by influencing the gene expression via the cAMP and downstream transcription factor CRE pathway	Fingolimod (FTY720) is an orally active immunomodulatory drug that has been used for the treatment of relapsing-remitting multiple sclerosis.	27913115	Details
Gsk3b	lithium chloride	inhibitor	experimental autoimmune encephalomyelitis	C57Bl/6J	The use of Lithium Chloride can increase stem cells differentiation into oligodendrocytes and improve re-myelination in MS.	The application of neuroprotective agents in combination with stem cells is considered a potential effective treatment for multiple sclerosis (MS).	36526850	Details
Act1	SRSF10	inhibitor	experimental autoimmune encephalomyelitis	C57Bl/6J	These findings suggest that TRAF3IP2-AS1 and/or SRSF10 may represent attractive therapeutic targets in the treatment of IL-17?related autoimmune diseases, such as psoriasis and multiple sclerosis.	IL-17A plays an essential role in the pathogenesis of many autoimmune diseases, including psoriasis and multiple sclerosis. Act1 is a critical adaptor in the IL-17A signaling pathway.	33941656	Details
S1pr1	Fingolimod	activator	experimental autoimmune encephalomyelitis	C57Bl/6J	In summary, we uncovered a broader cellular and therapeutic operation mode of FTY720, suggesting beneficial FTY720 effects also on CNS neurons during MS therapy and for treatment of other neurodegenerative diseases FTY720 effects also on CNS neurons during MS therapy and for treatment of other neurodegenerative diseases	Fingolimod (FTY720) is a new generation oral treatment for multiple sclerosis (MS). So far, FTY720 was mainly considered to target trafficking of immune cells but not brain cells such as neurons.	26980486	Details
Gna12	Fingolimod	activator	experimental autoimmune encephalomyelitis	C57Bl/6J	In summary, we uncovered a broader cellular and therapeutic operation mode of FTY720, suggesting beneficial FTY720 effects also on CNS neurons during MS therapy and for treatment of other neurodegenerative diseases FTY720 effects also on CNS neurons during MS therapy and for treatment of other neurodegenerative diseases	Fingolimod (FTY720) is a new generation oral treatment for multiple sclerosis (MS). So far, FTY720 was mainly considered to target trafficking of immune cells but not brain cells such as neurons.	26980486	Details
Gna13	Fingolimod	activator	experimental autoimmune encephalomyelitis	C57Bl/6J	In summary, we uncovered a broader cellular and therapeutic operation mode of FTY720, suggesting beneficial FTY720 effects also on CNS neurons during MS therapy and for treatment of other neurodegenerative diseases FTY720 effects also on CNS neurons during MS therapy and for treatment of other neurodegenerative diseases	Fingolimod (FTY720) is a new generation oral treatment for multiple sclerosis (MS). So far, FTY720 was mainly considered to target trafficking of immune cells but not brain cells such as neurons.	26980486	Details
Rhoa	Fingolimod	activator	experimental autoimmune encephalomyelitis	C57Bl/6J	In summary, we uncovered a broader cellular and therapeutic operation mode of FTY720, suggesting beneficial FTY720 effects also on CNS neurons during MS therapy and for treatment of other neurodegenerative diseases FTY720 effects also on CNS neurons during MS therapy and for treatment of other neurodegenerative diseases	Fingolimod (FTY720) is a new generation oral treatment for multiple sclerosis (MS). So far, FTY720 was mainly considered to target trafficking of immune cells but not brain cells such as neurons.	26980486	Details
Srf	Fingolimod	activator	experimental autoimmune encephalomyelitis	C57Bl/6J	In summary, we uncovered a broader cellular and therapeutic operation mode of FTY720, suggesting beneficial FTY720 effects also on CNS neurons during MS therapy and for treatment of other neurodegenerative diseases FTY720 effects also on CNS neurons during MS therapy and for treatment of other neurodegenerative diseases	Fingolimod (FTY720) is a new generation oral treatment for multiple sclerosis (MS). So far, FTY720 was mainly considered to target trafficking of immune cells but not brain cells such as neurons.	26980486	Details
SOCS1	Mannuronic Acid	activator	SPMS	NA	The gene expression of SOCS1, SOCS3, TRAF6 and SHIP1 were measured at the baseline and after 6 months of therapy with M2000, by using quantitative real-time PCR method.	The efficacy and safety of β-D-Mannuronic acid (M2000) as a novel immunosuppressive drug, patented (PCT/EP2017/067920), has been shown in experimental model of MS and also in a phase II clinical trial.	33908653	Details
SOCS3	Mannuronic Acid	activator	SPMS	NA	The gene expression of SOCS1, SOCS3, TRAF6 and SHIP1 were measured at the baseline and after 6 months of therapy with M2000, by using quantitative real-time PCR method.	The efficacy and safety of β-D-Mannuronic acid (M2000) as a novel immunosuppressive drug, patented (PCT/EP2017/067920), has been shown in experimental model of MS and also in a phase II clinical trial.	33908653	Details
INPP5D	Mannuronic Acid	activator	SPMS	NA	The gene expression of SOCS1, SOCS3, TRAF6 and SHIP1 were measured at the baseline and after 6 months of therapy with M2000, by using quantitative real-time PCR method.	The efficacy and safety of β-D-Mannuronic acid (M2000) as a novel immunosuppressive drug, patented (PCT/EP2017/067920), has been shown in experimental model of MS and also in a phase II clinical trial.	33908653	Details
Itga4	natalizumab	inhibitor	experimental autoimmune encephalomyelitis	C57Bl/6J	Collectively, these results suggest that the pri-mary action of natalizumab is interference with T cell extravasation via inhibition of α4β1 integrins.	inhibiting the α4 subunit of the integrin heterodimers α4β1 and α4β7 with the monoclonal antibody natalizumab is an effective treatment for multiple sclerosis (MS).	19179279	Details
Alox5	MK886	inhibitor	experimental autoimmune encephalomyelitis	C57Bl/6J	Thus, 5-LO inhibition may be a useful therapeutic treatment in demyelinating diseases of the CNS	Increased expression of 5-lipoxygenase (5-LO), a key enzyme in the biosynthesis of leukotrienes (LTs), has been reported in MS lesions and LT levels are elevated in the cerebrospinal fluid of MS patients.	21555210	Details
FOXP3	rapamycin	activator	RRMS	NA	The expression rate of FOXP3 and GARP genes in regulatory T cells increased after the therapy which could favor the treatment of MS.	The routine therapies for relapsing-remitting multiple sclerosis (RRMS) are common disease-modifying, yet are not effective in all patients.	30219744	Details
LRRC32	rapamycin	activator	RRMS	NA	The expression rate of FOXP3 and GARP genes in regulatory T cells increased after the therapy which could favor the treatment of MS.	The routine therapies for relapsing-remitting multiple sclerosis (RRMS) are common disease-modifying, yet are not effective in all patients.	30219744	Details
IL4	interleukin (IL)-4 -producing HSV-1 g134.5 deletion viruses	activator	MS	NA	The results indicate that the intracranial infection with IL-4-producing virus (1) precludes EAE symptoms, (2) protects the spinal cord from massive leukocyte infiltrations and (3) prevents demyelination and axonalloss	We have used interleukin (IL)-4 and -10-producing HSV-1 g134.5 deletion viruses in gene therapy of a BALB/c model of experimental allergic encephalomyelitis (EAE), a T cell-mediated demyelinating disease of the central nervous sys-tem	11420640	Details
Itga4	antisense oligonucleotides(ASO)	inhibitor	experimental autoimmune encephalomyelitis	C57Bl/6J	With the promising results in ameliorating disease progression, we are optimistic that the candidate oligomer may also be applicable to many other diseases associated with integrin alpha 4 mediated inflammation.	This highly specific strategy to down-regulate protein expression through interfering with normal exon selection during pre-mRNA processing should be applicable to many other gene targets that undergo splicing during expression	31506448	Details
Vegf	Adenoviral delivery of soluble VEGF receptor 1 (sFlt-1)	inhibitor	experimental autoimmune encephalomyelitis	C57Bl/6J	This study demonstrates that sFlt-1(1-3) gene transfer into the brain ameliorates the severity of EAE by inhibiting monocyte recruitment in the CNS of dark Agouti rats.	Previous studies have shown that vascular endothelial growth factor (VEGF) expression is up-regulated in both multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), a model for MS, and may exacerbate the disease.	18721816	Details
Rtn4	Bu Shen Yi sui capsule（BSYSC)	inhibitor	experimental autoimmune encephalomyelitis	C57Bl/6J	BSYSC could attenuate axonal injury and promote repair of axonal damage in EAE mice in part through the down-regulation of NogoA/NgR and RhoA/ROCK signaling pathways.	Axon growth inhibitory factors NogoA/Nogo receptor (NgR) and its signaling pathways RhoA/Rho kinase (ROCK) play a critical role in the repair of nerve damage in multiple sclerosis (MS). Bu Shen Yi Sui Capsule (BSYSC) is an effective Chinese formula utilized to treat MS in clinical setting and noted for its potent neuroprotective effects.	28668079	Details
Rtn4r	Bu Shen Yi sui capsule（BSYSC)	inhibitor	experimental autoimmune encephalomyelitis	C57Bl/6J	BSYSC could attenuate axonal injury and promote repair of axonal damage in EAE mice in part through the down-regulation of NogoA/NgR and RhoA/ROCK signaling pathways.	Axon growth inhibitory factors NogoA/Nogo receptor (NgR) and its signaling pathways RhoA/Rho kinase (ROCK) play a critical role in the repair of nerve damage in multiple sclerosis (MS). Bu Shen Yi Sui Capsule (BSYSC) is an effective Chinese formula utilized to treat MS in clinical setting and noted for its potent neuroprotective effects.	28668079	Details
Rhoa	Bu Shen Yi sui capsule（BSYSC)	inhibitor	experimental autoimmune encephalomyelitis	C57Bl/6J	BSYSC could attenuate axonal injury and promote repair of axonal damage in EAE mice in part through the down-regulation of NogoA/NgR and RhoA/ROCK signaling pathways.	Axon growth inhibitory factors NogoA/Nogo receptor (NgR) and its signaling pathways RhoA/Rho kinase (ROCK) play a critical role in the repair of nerve damage in multiple sclerosis (MS). Bu Shen Yi Sui Capsule (BSYSC) is an effective Chinese formula utilized to treat MS in clinical setting and noted for its potent neuroprotective effects.	28668079	Details
Rock1	Bu Shen Yi sui capsule（BSYSC)	inhibitor	experimental autoimmune encephalomyelitis	C57Bl/6J	BSYSC could attenuate axonal injury and promote repair of axonal damage in EAE mice in part through the down-regulation of NogoA/NgR and RhoA/ROCK signaling pathways.	Axon growth inhibitory factors NogoA/Nogo receptor (NgR) and its signaling pathways RhoA/Rho kinase (ROCK) play a critical role in the repair of nerve damage in multiple sclerosis (MS). Bu Shen Yi Sui Capsule (BSYSC) is an effective Chinese formula utilized to treat MS in clinical setting and noted for its potent neuroprotective effects.	28668079	Details
Gper1	G-1	activator	experimental autoimmune encephalomyelitis	C57Bl/6J	This study is the first to evaluate the protective effect of GPR30 activation on EAE, and provides a strong foundation for the clinical application of GPR30 agonists such as G-1 in MS.	Treatment with G-1, an agonist that selectively activates GPR30 without engagement of the iERs, retained estradiol's ability to protect against clinical and histological EAE without estradiol-associated side effects, deviated cytokine profiles and enhanced suppressive activity of CD4+Foxp3+ Treg cells through a GPR30- and programmed death 1 (PD-1)-dependent mechanism	19234228	Details
Adh5	N6022	activator	experimental autoimmune encephalomyelitis	C57Bl/6J	The data presented here provide evidence of the role of GSNO in shifting B cell immune balance (IL-10 >IL-6) and the preclinical relevance of N6022, a first-in-class drug targeting GSNOR with proven human safety, as therapeutics for autoimmune disorders including multiple sclerosis.	the GSNO/N6022-mediated regu-lation of IL-10 vs. IL-6 was not limited to regulatory B cells but also to a broad range of B cell subsets and antibody-secreting cells.	34175668	Details
Itga4	antisense oligonucleotides(ASO)	inhibitor	experimental autoimmune encephalomyelitis	C57Bl/6J	With the promising results in ameliorating disease progression, we are optimistic that the candidate oligomer may also be applicable to many other diseases associated with integrin alpha 4 mediated inflammation.	This highly specific strategy to down-regulate protein expression through interfering with normal exon selection during pre-mRNA processing should be applicable to many other gene targets that undergo splicing during expression	31506448	Details
Vegf	Adenoviral delivery of soluble VEGF receptor 1 (sFlt-1)	inhibitor	experimental autoimmune encephalomyelitis	C57Bl/6J	This study demonstrates that sFlt-1(1-3) gene transfer into the brain ameliorates the severity of EAE by inhibiting monocyte recruitment in the CNS of dark Agouti rats.	Previous studies have shown that vascular endothelial growth factor (VEGF) expression is up-regulated in both multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), a model for MS, and may exacerbate the disease.	18721816	Details
IL6	Vitamin D	activator	MS	RRMS	Significant up-regulation of IL-6 and IL-17A gene expression was shown under vitamin D treatment.	Vitamin D regulates gene expression and affects target cell functions. IL-6 and IL-17A are pro-inflammatory cytokines associated with MS pathogenesis.	26188623	Details
IL-17A	Vitamin D	activator	MS	RRMS	Significant up-regulation of IL-6 and IL-17A gene expression was shown under vitamin D treatment.	Vitamin D regulates gene expression and affects target cell functions. IL-6 and IL-17A are pro-inflammatory cytokines associated with MS pathogenesis.	26188623	Details
Rorc	RORγT inhibitors.	inhibitor	experimental autoimmune encephalomyelitis	C57Bl/6J	Guo et al. find that small-molecule RORgT antagonist treatment induces CD4+CD8+ thymocyte apoptosis, skews the T cell repertoire, prevents autoreactive T cell development, and delays autoimmune EAE progression.	Thus, targeting RORgT not only inhibits Th17 cell development and function but also fundamentally alters thymic-emigrant recognition of self and foreign antigens.The analysis of RORg inhibitors has allowed us to gain a broader perspective of the diverse function of RORgT and its impact on T cell biology	28009290	Details
Mir20a	miR-20a antagomirs	inhibitor	experimental autoimmune encephalomyelitis	C57Bl/6J	miR-20a suppresses the differentiation of antigen-specific CD4+ T cells into Tregs in EAE by decreasing the expression of Map3k9. miR-20a antagomirs alleviate EAE, suggesting a new therapy for EAE and CNS inflammatory demyelinating diseases.	Experimental autoimmune encephalomyelitis (EAE) is a model for inflammatory demyelinating dis-eases of the central nervous system (CNS), a group of autoimmune diseases characterized by inflammatory infiltra-tion, demyelination, and axonal damage. miR-20a is dysregulated in patients with CNS inflammatory demyelinating diseases; however, the function of miR-20a remains unclear. In this study, we intended to explore the role of miR-20a in EAE.	34039371	Details
ADA	cladribine tablet	inhibitor	MS	MS	The selective targeting of the ADA pathway through cladribine tablet therapy could be effective in MS by acting on a pathogenically relevant biological mechanism.	The immune response homeostasis is crucially regulated by the activity of the enzyme adenosine deaminase (ADA), as evidenced in patients with genetic ADA deficiency and in those treated with cladribine tablets.	33007809	Details
Rorc	DDC	activator	experimental autoimmune encephalomyelitis	C57Bl/6J	In conclusion, our study provides a scientific basis that DDC, as an inverse agonist of RORγt with simple structure, rich sources, low cost, high efficiency, and low toxicity, has great potential for the development of a novel effective immunomodulator for the treatment of Th17-mediated inflammatory diseases.	Multiple sclerosis, inflammatory bowel disease and organ transplant rejection are related to Th17 cell development and inflammatory respond. RORγt, a specific transcription factor regulating Th17 cell differentiation, is a pivotal target for the treatment of diseases.	35453073	Details
MIR26A1	INF-β	inhibitor	MS	MS	Afterward, we have evaluated in blood platelets from interferon-β treated Multiple Sclerosis patients the expression of miR-26a and SLC1A1, finding not only their converse expression, but also a responsiveness to interferon-β therapy	We have already found that the expression of a specific miRNA, hsa-mir-26a-5p (miR-26a), changed during INF-β treatment in responder Relapsing-Remitting MS patients.	28962897	Details
SLC1A1	INF-β	inhibitor	MS	MS	Afterward, we have evaluated in blood platelets from interferon-β treated Multiple Sclerosis patients the expression of miR-26a and SLC1A1, finding not only their converse expression, but also a responsiveness to interferon-β therapy	We have already found that the expression of a specific miRNA, hsa-mir-26a-5p (miR-26a), changed during INF-β treatment in responder Relapsing-Remitting MS patients.	28962897	Details
CXCL10	AS-POcrg2	inhibitor	MS	MS	The antisense treatment did not alter inflammation of the spinal cord. While AS-PS oligonucleotides were unsuitable for intrathecal administration, AS-POcrg2 were not toxic and reduced paralysis due to EAE.	The role of CRG-2 protein (murine IP-10) in experimental allergic encephalomyelitis (EAE), an animal model of multiple sclerosis, was tested by blocking crg-2 mRNA synthesis using chronic infusion of antisense oligonucleotides into lumbar subarachnoid space by osmotic minipumps.	8764376	Details
NCOA7	Interferon b-1b	activator	MS	MS	We describe a new role for IFN-bs involving a mechanism of action that leads to an increase in resistance to inflammation-mediated oxidative stress.	We demonstrate that interferon (IFN)-b-1b induces an alternative-start transcript containing the C-terminal TLDc domain of nuclear receptor coactivator protein 7 (NCOA7), a member of the OXR family of oxidation resistance proteins.	25330068	Details
Il-10	IFNb	activator	experimental autoimmune encephalomyelitis	C57Bl/6J	Together, results from this study suggest that IFNb may induce antigen-specific T cells to produce IL-10, which in turn negatively regulate Th17-mediate inflammatory and autoimmune response.	Whereas the immune system is essential for host defense against pathogen infection or endogenous danger signals,dysregulated innate and adaptive immune cells may facilitate harmful inflammatory or autoimmune responses	22163016	Details
Yap1	XMU-MP-1	activator	experimental autoimmune encephalomyelitis	C57Bl/6J	activation of YAP signaling by XMU-MP-1 relieved the neuroinflammation and demyelination in optic nerve of EAE mice.	Taken together, these results indicated that activation of YAP signaling by XMU-MP-1 could reduce inflammatory infiltration and demyelination and the loss of RGCs in EAE mice through upregulating the TGF-β signaling.	34373754	Details
Yap1	SRI-011381	activator	experimental autoimmune encephalomyelitis	C57Bl/6J	SRI-011381 partially rescued the deficits in optic nerve and retina of YAPGFAP-CKO EAE mice	Taken together, these results indicate that activation of TGF-β signaling pathway partially relieves the neuroinflammation and demyelination in optic nerve and retina of YAPGFAP-CKO EAE mice.	34373754	Details
Ggt1	Acivicin	inhibitor	experimental autoimmune encephalomyelitis	C57Bl/6J	identified the glutathione regulating compound acivicin with potent therapeutic effects in chronic and relapsing multiple sclerosis (MS) models	By GGT activity assay and quantitative real-time cell imaging of intracellular glutathione37, we showed that fibrin increased GGT activity and induced degradation of glutathione (Fig. 6b, c and Extended Data Fig. 6a,b). Acivicin and GGsTop restored glutathione levels in fibrin-treated macrophages and decreased ROS production	32284594	Details
B4galt6	PDMP	inhibitor	experimental autoimmune encephalomyelitis	NOD mice	B4GALT5/6 inhibition suppresses astrocyte activation in EAE	B4GALT5/6 inhibition by PDMP reduced the expression of demyelination-associated genes and increased the expression of remyelination-associated genes	25216636	Details
Ido1	INCB024360	inhibitor	experimental autoimmune encephalomyelitis	C57Bl/6J	The administration of IDO inhibitor (INCB024360) was able to alleviate weight loss, clinical signs and blunting inflammatory process, suggesting that the increase in IDO/KMO activity and mRNA levels are involved in the severity of the clinical course of EAE.	Evidence has suggested that the activation of indoleamine-2,3-dioxygenase (IDO), the rate-limiting enzyme in the kynurenine pathway (KP), plays a crucial role in inflammation-related diseases.	33040279	Details
Il-12 a	DMF, dimethylfumarate	inhibitor	experimental autoimmune encephalomyelitis	C57Bl/6J	This therapeutic approach improves Th1- and Th17-mediated autoimmune diseases such as psoriasis and MS by interfering with IL-12 and IL-23 production.	Type II DCs result from fumarate- induced glutathione (GSH) depletion, followed by increased hemoxygenase-1 (HO-1) expression and impaired STAT1 phosphorylation. Induced HO-1 is cleaved, whereupon the N-terminal fragment of HO-1 translocates into the nucleus and interacts with AP-1 and NF-B sites of the IL-23p19 promoter. This interaction prevents IL-23p19 transcription without affecting IL-12p35, whereas STAT1 inactivation prevents IL-12p35 transcription without affecting IL-23p19.	21987655	Details
Il-23 a	DMF, dimethylfumarate	inhibitor	experimental autoimmune encephalomyelitis	C57Bl/6J	This therapeutic approach improves Th1- and Th17-mediated autoimmune diseases such as psoriasis and MS by interfering with IL-12 and IL-23 production.	Type II DCs result from fumarate- induced glutathione (GSH) depletion, followed by increased hemoxygenase-1 (HO-1) expression and impaired STAT1 phosphorylation. Induced HO-1 is cleaved, whereupon the N-terminal fragment of HO-1 translocates into the nucleus and interacts with AP-1 and NF-B sites of the IL-23p19 promoter. This interaction prevents IL-23p19 transcription without affecting IL-12p35, whereas STAT1 inactivation prevents IL-12p35 transcription without affecting IL-23p19.	21987655	Details
C3	AA v - crry	inhibitor	experimental autoimmune encephalomyelitis	C57Bl/6J	AA V-Crry treatment significantly blocked loss of visual acuity in mice at both the onset and peak of EAE.	Viral overexpression of the complement inhibitor Crry at C3-bound synapses decreased microglial engulfment of synapses and protected visual function.	31883839	Details
Ehmt2	UNC0642	inhibitor	experimental autoimmune encephalomyelitis	C57Bl/6J	In line with these findings, we found a potent neuroprotective effect of pharmacological G9a inhibition manifesting in increased neuro-nal survival and improved clinical outcome in CNS inflammation.	G9a activity repressed anti-ferroptotic genes, diminished intracellular glutathione levels, and triggered the iron-dependent programmed cell death pathway ferroptosis	35930635	Details
Pparg	ursolic acid	activator	experimental autoimmune encephalomyelitis	C57Bl/6J	Oral treatment with UA significantly decreased disease severity and CNS inflammation and demyelination in experimental autoimmune encephalomyelitis (EAE), an animal model of MS.	Mechanistically, UA induced promyelinating neurotrophic factor CNTF in astrocytes by peroxisome proliferator-activated receptor γ(PPARγ)/CREB signaling, as well as by up-regulation of myelin-related gene expression during oligodendrocyte maturation via PPARγ activation.	32253301	Details
Cntf	ursolic acid	activator	experimental autoimmune encephalomyelitis	C57Bl/6J	Oral treatment with UA significantly decreased disease severity and CNS inflammation and demyelination in experimental autoimmune encephalomyelitis (EAE), an animal model of MS.	Mechanistically, UA induced promyelinating neurotrophic factor CNTF in astrocytes by peroxisome proliferator-activated receptor γ(PPARγ)/CREB signaling, as well as by up-regulation of myelin-related gene expression during oligodendrocyte maturation via PPARγ activation.	32253301	Details
Il21	AAV8.sIL21R	inhibitor	experimental autoimmune encephalomyelitis	C57Bl/6J	Although the administration of the treatment during the development of the immune response was counterproductive, the preventive administration of the therapeutic vectors showed a protective effect by reducing the number of animals that developed the disease, as well as an improvement at the histopathological level and a modification of the immunological profile of the animals treated with the AAV8.sIL21R.	The pathogenic role of the interleukin 21 (IL-21) in different autoimmune diseases, such as multiple sclerosis (MS), has been extensively studied.	35902536	Details
Mapk3	tyrphostin A9	activator	experimental autoimmune encephalomyelitis	C57Bl/6J	In the relapsing-remitting EAE model, oral administration of A9 successfully ameliorated clinical symptoms, activated ERK1/2, induced axonal protection, and increased the abundance of the regeneration biomarker GAP-43 in the CNS.	Activation of ERK1/2 is necessary and sufficient for nerve growth factor (NGF)-induced PC12 cell differentiation [10]. It can protect neurons from apoptosis due to injury or toxicity [11,12,13] and is involved in promoting neuronal survival	35143827	Details
Nrg1	HBD-SH4	inhibitor	experimental autoimmune encephalomyelitis	C57Bl/6J	In conclusion,expression of neuregulin antagonist in the brain and spinal cord protects females but not males, suggesting a complex interplay between NRG1 and sex difference in EAE that may be associated with microglia-mediated inflammation.	We previously reported that a targeted NRG1 antagonist (HBD-S- H4) given intrathecally, reduces inflammatory microglial activation in a spinal cord pain model and a neuro- degenerative disease mouse model in vivo, suggesting that it may have effects in neuroninflammatory and neuronal disorders.	29534847	Details
Maf	methyl butyrate (MB)	activator	experimental autoimmune encephalomyelitis	C57Bl/6J	we found that MB treatment upregulated Maf gene expres-sion in mice, which explained its promotion of IL-10 secretion.	MB Treatment Promotes Treg Development and IL10 Secretion in Draining Lymph Nodes of EAE Mice	34786625	Details
Tgfb1	orexin-A (OX-A)	activator	experimental autoimmune encephalomyelitis	C57Bl/6J	However, administration of OX-A or SB (30 nmol) in EAE induced mice increased and decreased the expression of TGF-β1 mRNA,respectively compared to the EAE group.	NA	26857503	Details
Nos2	orexin-A (OX-A)	inhibitor	experimental autoimmune encephalomyelitis	C57Bl/6J	Administration of OX-A or SB (30 nmol) in EAE induced mice decreased and increased the expression of iNOS mRNA compared to EAE group, respectively	NA	26857503	Details
Mmp-9	orexin-A (OX-A)	inhibitor	experimental autoimmune encephalomyelitis	C57Bl/6J	Administration of OX-A decreased the expression of MMP-9 mRNA compared to the EAE group	NA	26857503	Details
Mbp	orexin-A (OX-A)	activator	experimental autoimmune encephalomyelitis	C57Bl/6J	Administration of OX-A or SB (30 nmol) in EAE induced mice in- creased and decreased the expression of MPB mRNA compared to the EAE group, respectively (F(8, 48) = 22.738; all p b 0.05)	NA	26857503	Details
Il12b	orexin-A (OX-A)	inhibitor	experimental autoimmune encephalomyelitis	C57Bl/6J	Administration of OX-A decreased the expression of IL-12 mRNA	NA	26857503	Details
Ccr2	orexin-A (OX-A)	activator	experimental autoimmune encephalomyelitis	C57Bl/6J	compared to the EAE group (F(8, 48) = 6 . 1 2 1 ; p = 0 . 0 0 8 )	NA	26857503	Details
Tlr2	Toll-like receptor 2 and 4 antagonism	inhibitor	experimental autoimmune encephalomyelitis	C57BL/6J	The data demonstrated that blocking TLR2/TLR4 suppressed EAE-related pain, equally in males and females; upregulation of dorsal spinal cord proinflammatory gene expression for TLR2, TLR4, NLRP3, interleukin-1β, IkBα, TNF-α and interleukin-17; and upregulation of dorsal spinal cord expression of glial immunoreactivity markers.	Toll-like receptors 2 and 4 (TLR2/TLR4) have emerged as targets for treating a wide array of autoimmune disorders, including MS, as well as having demonstrated success at suppressing pain in diverse animal models.	33358978	Details
Il1r1	interleukin-1 receptor antagonist	inhibitor	experimental autoimmune encephalomyelitis	C57BL/6J	In support of these results, intrathecal interleukin-1 receptor antagonist reversed EAE-induced allodynia, both early and late after EAE induction.	NA	33358978	Details
Elavl1	anti-HuR antisense oligonucleotide (ASO)	inhibitor	experimental autoimmune encephalomyelitis	C57BL/6J	Mice that received anti-HuR ASO exhibited improved EAE-related motor dysfunction, pain hypersensitivity, and body weight loss.	NF-κB Activation Was Reduced by HuR Silencing	33200288	Details
Il-23 a	RIL-23R	inhibitor	experimental autoimmune encephalomyelitis	C57BL/6J	The transfection of RIL-23R mRNA improved MSC properties significantly to the inflamed regions of EAE mice, and it performed an increased suppressive function on the T lymphocyte proliferation	Interleukin 23 (IL-23), which belongs to the interleukin 12 families, plays a vital role in the proliferation of T lymphocytes. Two dif- ferent subunits (specific subunit: IL23A or IL-23p19) and general subunit (IL12Rβ1) are found in the structure of het- erodimer receptors of this cytokine [4]. In addition, Th17 cells secrete IL-17 and IL-23 under the influence of vari- ous factors, including the transforming growth factor-beta (TGF-β) and IL-6. These cytokines lead to Th17 and Th1 cell activation, development of inflammation, and suppres- sion of the immune system	35325396	Details
Gdnf	GDNF / NSCs	inhibitor	EAE	N/A	The rats that received NSCs recovered their normal gait at 50 days after EAE induction, whereas the rats receiving GDNF/NSCs recovered at 45 days after EAE induction.	In summary, we showed here that GDNF/NSCs grafting significantly promotes functional recovery in EAE rats, reducing brain inflammatory infiltration, improving density of myelin, increasing repopulation of neurons and oligodendrocyte lineage cells, and decreasing the astrocyte differentiation of NSCs.	27212951	Details
Nr4a2	isoxazolo-pyridinone 7e	inhibitor	EAE	N/A	In the preventive treatment, immunized mice received the compound via gavage beginning from the 7th d.p.i., when phenotypic EAE signs are not yet evident but the immunization process has already occurred. The analysis revealed that the IP7e preventive treatment was able to delay the disease progression.	A potential mechanism at the basis of the improvement of EAE observed after the preventive IP7e treatment could be represented by the block in the early phase of the disease of the pro-inflammatory NF-kB pathway by Nurr1 signalling activation.	25265488	Details
Cd44	PH20 hyaluronidase	inhibitor	EAE	N/A	These improved symptoms correspond histologically to degradation of HA in the lumen of CNS blood vessels, decreased demyelination, and impaired CD4(+) T-cell extravasation.	In conclusion we have demonstrated that standard CD44 on CNS ECs but not activated lymphocytes contributes to lymphocyte rolling on the endothelial surface. These findings expand the knowledge of mechanisms promoting inflammatory demyelinating CNS disease and suggest that HA anchored to EC CD44 represents a therapeutic target to reduce immune cell infiltration into the brain.	22865853	Details
Il18	DT390-IL-18	inhibitor	EAE	N/A	This study suggested that the recombinant immunotoxin DT390-IL-18 could be expressed in vitro and in vivo, and prevented murine EAE effectively.	We speculate that depletion of other IL-18–expressing cells may contribute to suppression of EAE, but the effect was limited.	18346003	Details
Pparg	PPAR-gamma ligand 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ2)	inhibitor	EAE	N/A	Administration of 15d-PGJ2 before and at the onset of clinical signs of EAE significantly reduced the severity of disease.	Initial studies have shown that the presence of the PPAR-gamma ligand 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ2) inhibits the proliferation of Ag-specific T cells from the spleen of myelin basic protein Ac(1-11) TCR-transgenic mice. 15d-PGJ2 suppressed IFN-gamma, IL-10, and IL-4 production by both Con A- and myelin basic protein Ac(1-11) peptide-stimulated lymphocytes as determined by ELISA and ELISPOT assay.	11859145	Details
Ifnb1	type I IFN mimetic	inhibitor	EAE	N/A	The observation that the type I IFN mimetic was therapeutically effective against EAE, but lacked the toxicity associated with the intact IFN suggests that the two events are not associated.	The complex formation and the functional cytoplasmic activity of IFN truncations thus show similarities in complexity to that of steroid signaling	23110939	Details
ASIC1	amiloride	inhibitor	MS	PPMS	Our results extend evidence of the contribution of ASIC1 to neurodegeneration in multiple sclerosis and suggest that amiloride may exert neuroprotective effects in patients with progressive multiple sclerosis.	N/A	23365093	Details
Ccl2	P8A-CCL2	inhibitor	EAE	N/A	P8A-CCL2 administration, however, decreased demyelination, axonal loss and number of CNS infiltrating T cells and macrophages.	Immunological analysis revealed that P8A-CCL2 does not act on Ag-specific T cell proliferation and does not interfere with the differentiation of IFNgamma-releasing effectors T cells. These results suggest that the therapeutic mechanism of P8A-CCL2 may rely on interference with immune cell recruitment.	19232440	Details
IFNB1	Interferon-beta	inhibitor	MS	RRMS	Peripheral blood samples were obtained from 16 patients before and after 3, 6 and 12 months of IFNbeta1b treatment. Eleven patients did not have any clinical relapse, whereas the other five each had one clinical exacerbation during the study.	IFNbeta1b treatment was unable to restore the initial low mitogen-induced production of IL-10; only after 1 year of therapy was a slight increase observed. Cytokine therapy did not affect the mitogen-induced production of TGFbeta1.	11054484	Details
Cx3cr1	TAM	inhibitor	EAE	N/A	The only difference in this experimental system was that TAM-treated mice exhibited a slight delay in EAE and a trend for reduced clinical scores compared to vehicle-treated mice in the acute phase (Figure 1C), which we found to associate with an unanticipated effect of the TAM in inhibiting myelin-specific Th17 responses and immune cell accumulation in the CNS.	It is also possible that the escalation in inflammation just occurred as a secondary consequence of the increased myelin and neuronal damage in the CNS of Cx3cr1CreERT2:Ppardfl/fl mice.	33732230	Details
GPR183	Natalizumab	inhibitor	MS	RRMS	We observed that EBI2 is functionally expressed on memory CD4 T cells and is enhanced under natalizumab treatment.	These data suggest a significant role for EBI2 in human CD4 T cell migration, notably in patients with MS.	28052250	Details
Tlr8	1,25-Dihydroxyvitamin D3	inhibitor	EAE	N/A	1,25(OH)2D3 Treatment Reduced Inflammatory Cell Infiltration and Inflammatory Cytokine Expression in the EAE Spinal Cord	In summary, our novel findings suggest that TLR8 is a new target of 1,25(OH)2D3 and may mediate the anti-inflammatory action of 1,25(OH)2D3. Our findings also point to a destructive role of TLR8 in EAE and shed lights on pathogenesis of multiple sclerosis.	23516559	Details
Pparg	troglitazone	inhibitor	EAE	N/A	The expression of PPAR-γ mRNA in troglitazone-treated group was increased comparing with that of vehicle-treated group. This finding suggests that troglitazone increases PAR-γ transcription in vivo.	Thus, troglitazone treatment appeared to result in the enhanced expression of PPAR-γ message and reduced expressions of the pro-inflammatory cytokines, IL-1b and TNF-a messages,in the spinal cords.	11311328	Details
CNR1	interferon-β	inhibitor	MS	RRMS	CB1 expression was elevated in all cell subsets	The different expression of cannabinoid receptor genes and the increased level of AEA in lymphocytes point to a possible role of the cannabinoid system in MS immune response and its modulation by interferon.	25169051	Details
CNR2	interferon-β	inhibitor	MS	RRMS	CB1 expression was elevated in all cell subsets	The different expression of cannabinoid receptor genes and the increased level of AEA in lymphocytes point to a possible role of the cannabinoid system in MS immune response and its modulation by interferon.	25169051	Details
Ifnb1	MSCs-IFN β	inhibitor	EAE	N/A	Importantly, injected MSCs-IFN β migrated into inflamed CNS and significantly reduced further injury of blood-brain barrier (BBB) permeability in EAE mice.	In conclusion, this study demonstrated that hBM-MSCs can be used as a new delivery vehicle for IFN-β therapy against EAE, and MSCs-IFNβ exhibit strong therapeutic effects by decreasing inflammatory cell influx, suppressing demyelination and immunomodulatory effects by promoting a shift from the Th1 to the Th2 cytokine balance, stabilizing the BBB and preventing the progression of disease in EAE mice.	23710456	Details
Ltbr	LTbetaR-Ig	inhibitor	EAE	RREAE	The present findings indicate that both LTbeta and LTbetaR are upregulated at EAE onset and during subsequent relapses and that systemic and local blockade of the LT pathway with LTbetaR-Ig results in protracted and transient inhibition of EAE clinical signs, respectively.	LTbetaR-Ig treatment also reduces T- and B-cell infiltration and prevents the induction of the chemokines CXCL10 and CXCL13 and the formation of organized ectopic follicles in the EAE-affected CNS.	16870269	Details
PPARG	pioglitazone	inhibitor	MS	N/A	Effect of PIO treatment on PPAR-γDNA-binding activity and NF-kB DNA-binding activity in PBMCs from MS patients	In MS patients, pioglitazone-induced increase in PPAR-gamma DNA-binding activity and decrease in NF-kappaB DNA-binding activity was only observed in the absence of an acute MS relapse.	16210596	Details
Tnf	dTNFR	inhibitor	EAE	N/A	These levels of dTNFR protein were biologically active and could significantly ameliorate both acute and relapsing EAE.	This cell-based gene-vector approach is ideal for delivering proteins to the CNS and has particular relevance to the control of inflammatory CNS disease.	10679120	Details
Nfe2l2	dimethyl fumarate	inhibitor	EAE	N/A	We show here that dimethyl fumarate (DMF) dose-dependently induces mitochondrial biogenesis and function dosed to cells in vitro, and also dosed in vivo to mice and humans.	Thus, DMF induces mitochondrial biogenesis primarily through its action on Nrf2, and is the first drug demonstrated to increase mitochondrial biogenesis with in vivo human dosing.	28460056	Details
NFE2L2	dimethyl fumarate	inhibitor	MS	N/A	We show here that dimethyl fumarate (DMF) dose-dependently induces mitochondrial biogenesis and function dosed to cells in vitro, and also dosed in vivo to mice and humans.	Thus, DMF induces mitochondrial biogenesis primarily through its action on Nrf2, and is the first drug demonstrated to increase mitochondrial biogenesis with in vivo human dosing.	28460056	Details
MS4A1	rituximab	inhibitor	MS	RRMS	Future studies will involve the administration of antibodies against CD20 by gene therapy and studying and characterizing the administration of multiples drugs, in combination rituximab, for treating MS.	Rituximab depletes peripheral B cells and reduces the level of B cells in the cerebrospinal fluid of patients with relapsing-remitting MS.	21155688	Details
Tnf	TNF	inhibitor	EAE	N/A	Furthermore, treatment with TNF dramatically reduces disease severity in both TNF-/- mice and in other TNF+/+ mice highly susceptible to the MOG-induced disease.	These findings indicate that TNF is not essential for the induction and expression of inflammatory and demyelinating lesions, and that it may limit the extent and duration of severe CNS pathology.	9427610	Details
NDI1	vector sc-CBA-NDI1	inhibitor	EAE	DBA/1J mice	In conclusion, targeting the dysfunctional complex I using NDI1 gene can be an approach to address axonal and neuronal loss responsible for permanent disability in MS that is unaltered by current disease modifying drugs.	The 45% optic nerve axonal and 33% retinal ganglion cell (RGC) loss contributed to the permanent loss of visual function in EAE mice were ameliorated by NDI1-mediated prevention of mitochondrial cristae dissolution and improved mitochondrial homeostasis.	31900864	Details
Cd6	UMCD9	activor	EAE	Wild-type (WT) mice, CD6 KO mice, and CD6 humanized mice	A Mouse Anti-Human CD6 mAb Reverses EAE Progression in the CD6 Humanized Mice	N/A	28209777	Details
GFAP	ribavirin	inhibitor	EAE	(n = 6 within each group): control group (C), intact rats; EAE group, EAE was induced as described	The present study indicates that ribavirin may have the ability to attenuate astrocyte proliferation and glial scaring at the peak of the disease and modulate the astroglial response to EAE during the time-course of the disease.	N/A	22785017	Details
ABCB1	mitoxantrone	inhibitor	MS	n=121	In conclusion, SNPs in ABC-transporter genes may serve as pharmacogenetic markers associated with clinical response to MX therapy in multiple sclerosis.	ATP-binding cassette-transporters ABCB1 and ABCG2 represent multi-drug resistance mechanisms involved in active cellular MX efflux.	19605531	Details
ABCG2	mitoxantrone	inhibitor	MS	n=121	In conclusion, SNPs in ABC-transporter genes may serve as pharmacogenetic markers associated with clinical response to MX therapy in multiple sclerosis.	ATP-binding cassette-transporters ABCB1 and ABCG2 represent multi-drug resistance mechanisms involved in active cellular MX efflux.	19605531	Details
Abcb1b	mitoxantrone	inhibitor	EAE	N/A	In conclusion, SNPs in ABC-transporter genes may serve as pharmacogenetic markers associated with clinical response to MX therapy in multiple sclerosis.	ATP-binding cassette-transporters ABCB1 and ABCG2 represent multi-drug resistance mechanisms involved in active cellular MX efflux.	19605531	Details
Abcg2	mitoxantrone	inhibitor	EAE	N/A	In conclusion, SNPs in ABC-transporter genes may serve as pharmacogenetic markers associated with clinical response to MX therapy in multiple sclerosis.	ATP-binding cassette-transporters ABCB1 and ABCG2 represent multi-drug resistance mechanisms involved in active cellular MX efflux.	19605531	Details
Cnr1	cannabinoids	inhibitor	EAE	Biozzi ABH and ABH mice lacking the CB1 receptor (Cnr1) gene	Gene knockout technology provides an important tool in target validation and indicates that the CB1 receptor is the main cannabinoid target for an anti-spastic effect.	N/A	17220914	Details
Il4	immunomodulatory cytokine interleukin (IL)-4	inhibitor	EAE	N/A	Special emphasis is put on the use of non-replicative herpes simplex type-1 (HSV)-derived vectors engineered with the gene of the immunomodulatory cytokine interleukin (IL)-4.	N/A	10918474	Details
IRF5	IFN-b	inhibitor	MS	Peripheral blood	The combined analysis of available datasets yielded an effect size on MS with odds ratio (OR)MantelHaenszel 1.14 (Po0.002) for the IRF5 polymorphisms rs4728142 and rs3807306	1 IRF pathways also participate in the regulation of the antiviral innate response.2 IRF5-induced innate antiviral responses appear to result in a broad alteration of the transcriptional profile of cellular genes.3,4 IRF5 is expressed mainly in lymphocytes and dendritic cells, but it is induced in other cells in response to type I interferon (IFN)5	20861862	Details
IRF5	IFNb	inhibitor	MS	Peripheral blood	We found that patients with the IRF5 rs2004640-TT and rs47281420-AA genotype exerted a poor pharmacological response to IFNb compared with patients carrying the respective G-alleles (P 0.0006 and P 0.0023, respectively). Moreover, patients with the rs2004640-TT genotype developed more magnetic resonance imaging (MRI)-based T2 lesions during IFNb treatment (P 0.003). Accordingly, an association between MRI-based non-responder status and rs2004640-TT genotype was observed (P 0.010). For the rs4728142-AA genotype a trend of an association with more T2 lesions during IFNb treatment and MRI-based non-responder status was observed (P 0.103 and P 0.154, respectively).	Clinical non-responders were characterized by an increased expression of IFN response genes before the start of therapy, and a lack of a pharmacologically induced increase in IFN response gene activity. Because Interferon Regulatory Factor 5 (IRF5) is a master regulator of IFN-activity, we carried out a candidate gene study of IRF5 gene variants in relation to the pharmacological and clinical response upon IFNb treatment	21471993	Details
IFNAR1	IFNb	inhibitor	MS	CSF	In vivo recombinant IFN-b–1a treatment induced IFNAR1 and its downstream signaling molecules’ gene expression, suggesting that treatment reconstitutes a deficient endogenous IFN-b regulation of the CD4+ T cells’ pathogenic cytokine production in patients with MS.	We identified that the endogenous IFN-b from serum of RRMS patients induced a significantly lower IFN-inducible gene expression in comparison with healthy controls. In addition, in vitro studies have revealed deficient endogenous and exogenous IFN-b signaling in the CD4+ cells derived from patients with MS. Interestingly, upon inhibition of the endogenous IFN-b signaling by silencing IFN regulatory factor (IRF) 7 gene expression, the resting CD4+ T cells secreted significantly higher level of IL-17A, IL-17F, IL-21, IL-22, and IL-9, suggesting that endogenous IFN-b suppresses the secretion of these pathogenic cytokines.	24850724	Details
Plp1	teriflunomide	inhibitor	MS	Peripheral blood	Treatment of immune-incompetent PLP mutants did not provide evidence for a direct, neuroprotective effect of the medication. When treatment was terminated, no rebound of neuroinflammation occurred and histopathological improvement was preserved for at least 75 days without treatment. After disease onset, teriflunomide halted ongoing axonal perturbation and enabled a recovery of dendritic arborization by surviving ganglion cells. However, neither neuron loss nor clinical features were ameliorated, likely due to already advanced neurodegeneration before treatment onset.	Preventive treatment with teriflunomide attenuated the increase in number of CD8+ cytotoxic effector T cells and fostered the proliferation of CD8+ CD122+ PD-1+ regulatory T cells in the CNS	29970109	Details
TBX21	Silymarin	inhibitor	MS	Peripheral blood	IFN-γ level at a concentration of 100 μM in comparison with DMSO. Our findings here clearly show that silymarin is an effective regulator for Th1 response in vitro condition. It not only suppresses Th1 proliferating activity but also inhibits T-bet gene expression and IFN-γ production by these cells	T-bet gene expression was significantly decreased in Th1 cells isolated from newly diagnosed and IFN-β-treated RRMS patients after treatment with silymarin compared to DMSO control.	30178232	Details
Ltbr	vesnarinone	inhibitor	MS	glial cell	In the CNS, TNFa is produced by astrocytes and microglia (4). Microglia may be the main producer of TNFIx, because they respond to produce TNFcr much faster than astrocytes and respond to much lower concentration of lipopolysacclharide (LPS) than do astrocytes (4). In this study, we examined the effects ofvesnarinone on TNFa production by microglia. The effects on the other functions of microglia such as proliferation, expression of major histocompatibility complex antigen, enzyme activity and superoxide anion formation were also examined.	Tumor necrosis factor 01 (TNFcr) is considered to play a critical role in the development of various pathological processes in the central nervous system (CNS), such as neuronal degeneration, demyelination and gliosis. In order to search for agents which suppress TNFcx production in the CNS for future treatment of these pathological conditions, the effects of a synthetic oral inotropic agent, vesnarinone, on murine microglia were examined. Vesnarinone significantly suppressed TNFa production by microglia in a dose-dependent manner, without affecting their viability, enzyme activity or expression of the major histocompatibility complex.	10210262	Details
CD40	IFN	inhibitor	MS	peripheral blood	IFN-r treatment leads to the activation of NF-B in a time-dependent manner, which is inhibited in the presence of anti-TNF-β-neutralizing antibody. These results indicate that IFN-+-induced TNF-β production and subsequent NF-B activation are integral parts of the mechanism of IFN-+-induced CD40 expression	we have discovered that a major component of IFN-r-induced CD40 expression involves the endogenous production of the cytokine TNF-r. The inclusion of anti-TNF-r-neutralizing antibody significantly inhibits IFN-r-induced CD40 mRNA and CD40 promoter activity. IFN-r-induced CD40 protein expression is attenuated in TNF-r-deficient microglia and can be restored with exogenous TNF-r. Sitedirected mutagenesis studies demonstrate that three of the four NF-B elements in the CD40 promoter are required for IFN-r-induced CD40 promoter activity	11830590	Details
Mbp	curcumin	inhibitor	MS	spinal cord	The obtained results indicated it could be concluded that curcumin was able to improve EAE by increasing the amount of MBP gene expression and reducing the intensity of NOGO-A expression	Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis (MS). Previous studies have shown that myelin degradation during MS and EAE resulted in reduced expression of some of the proteins, e.g., the MBP (myelin basic protein), and increased expression of genes such as iNOS (Inducible nitric oxide synthase) and NOGO-A in the affected patients. In the present study, EAE was induced by immunizing Wistar rats (n=12) with homogenized spinal cord of guinea pig and Freund's complete adjuvant.	33953873	Details
Nos2	curcumin	inhibitor	MS	spinal cord	The obtained results indicated it could be concluded that curcumin was able to improve EAE by increasing the amount of MBP gene expression and reducing the intensity of NOGO-A expression	Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis (MS). Previous studies have shown that myelin degradation during MS and EAE resulted in reduced expression of some of the proteins, e.g., the MBP (myelin basic protein), and increased expression of genes such as iNOS (Inducible nitric oxide synthase) and NOGO-A in the affected patients. In the present study, EAE was induced by immunizing Wistar rats (n=12) with homogenized spinal cord of guinea pig and Freund's complete adjuvant.	33953873	Details
Rtn4	curcumin	inhibitor	MS	spinal cord	The obtained results indicated it could be concluded that curcumin was able to improve EAE by increasing the amount of MBP gene expression and reducing the intensity of NOGO-A expression	Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis (MS). Previous studies have shown that myelin degradation during MS and EAE resulted in reduced expression of some of the proteins, e.g., the MBP (myelin basic protein), and increased expression of genes such as iNOS (Inducible nitric oxide synthase) and NOGO-A in the affected patients. In the present study, EAE was induced by immunizing Wistar rats (n=12) with homogenized spinal cord of guinea pig and Freund's complete adjuvant.	33953873	Details
Nfe2l2	Tecfidera	activor	MS	C57BL/6J mice	our results suggested that MMF could potentially be used as a drug to minimize bone loss as a promising alternative to oral antioxidants. MMF activates endogenous antoxidant pathways like HO-1 and Nrf2, which allow the body to modulate levels of ROS with innate gene regulation and protein localization	The multiple sclerosis drug Tecfidera contains dimethylfumarate, which is rapidly metabolized to monomethylfumarate (MMF); MMF is thought to function through nuclear factor erythroid-derived-2-like-2 (Nrf2), a transcription factor activated by oxidative stress which induces the expression of endogenous antioxidant systems.	31362266	Details
Tnf	Ketamine	inhibitor	ischemic or traumatic brain injury	Male BALB/c mice	Ketamine inhibits endotoxin-induced NF-6B expression in brain cells in vivo and vitro and it is suggested that this may have implications in the neuroprotective effects of ketamine reported by other investigators	Ketamine suppressed endotoxin-induced neuronal NF-6B activation in a dose-dependent manner (P < 0.05, except for the 10–5M concentration in vitro) both in vivo and vitro	11032280	Details
KCNH1	EGCG	activor	MS	Male guinea pigs	ECGC has a number of electrophysiological effects in the heart, and these effects may have clinical significance when multigram doses of this compound are used in human clinical trials or through self-ingestion of large amounts of over-the-counter products enriched in EGCG	KvLQT1/minK K channel	20484151	Details
Hdac1	FTY720-Phosphate	activor	MS	LM/Bc mice	Elevated nuclear FTY720-P is associated with decreased HDAC activity and increased histone acetylation at H3K18 and H3K23 in LM/Bc MEFs. Treatment of LM/Bc MEFs with FTY720 and a selective Sphk2 inhibitor, ABC294640, significantly reduces the amount of FTY720-P that accumulates in the nucleus. The data provide insight into the relative amounts of FTY720-P generated in the nuclear versus cytoplasmic subcellular compartments after FTY720 treatment and the specific Sphk isoforms involved	The results of this study suggest that FTY720-induced NTDs may involve multiple mechanisms, including: (1) sustained and/or altered S1P receptor activation and signaling by FTY720-P produced in the cytoplasm and (2) HDAC inhibition and histone hyperacetylation by FTY720-P generated in the nucleus that could lead to epigenetic changes in gene regulation	26719367	Details
Nfe2l2	Abstract Dimethyl fumarate (DMF)	activor	MS	C57Bl/6N mice	Our findings suggest that DMF treatment confers neuroprotection after TBI via preservation of brain GSH levels rather than by modulating neuroinflammation.	DMF-treated mice displayed less neurological deficits than vehicle-treated mice and reduced histopathological brain damage.At the same time, the TBI-evoked depletion of brain GSH was prevented by DMF treatment.However, Nrf2 target gene mRNA expression involved in antioxidant and detoxifying pathways was increased in both treatment groups at 4 dal.	28921587	Details
Nos2	LX007	inhibitor	MS	C57/BL6J	We therefore conclude that LX007 exhibits anti-inflammatory effects in LPS-stimulated microglial cells by inhibiting pro-inflammatory mediators corresponding to the downregulating of MAPKs and NF-κB activation. Taken together, the present study indicated that LX007 may have potential to be developed into an anti-inflammatory agent in the future.	LX007 inhibited lipopolysaccharide (LPS)-stimulated nitric oxide (NO) and prostaglandin E2 (PGE2) expression, as well as their regulatory geneinducible NO syntheses (iNOS) and cyclooxygenase-2 (COX-2) in LPS-treated primary microglia. LPS-induced production from microglia of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF-α) was also significantly attenuated by LX007. Mechanistically, LX007 potently suppressed phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) p65 nuclear translocation in LPS-induced microglia.	29198015	Details
App	IFNβ	activor	AD	Adult male Wistar rats	Our results showed that over-expression of mutant human APP gene in the hippocampus led to learning and memory deficits concomitant with gliosis and pro-inflammatory responses.Interestingly, treatment of AD-modeled rats with IFNβ ameliorated memory impairments possibly through suppressing gliosis and shifting from pro-inflammatory toward anti-inflammatory status, suggesting that IFNβ may be a promising therapeutic agent to improve cognitive functions and modulate inflammatory responses in an AD-like neurodegenerative context.	Despite the fact that GFP expression level was lower than APP expression level, the lentiviral system used in this study resulted in an effective and widespread transduction of hippocampal neurons. Difference observed in expression of GFP and APP genes may be due to the particular position of these genes in FsynIGW lentiviral vector. As shown in Fig. 2A, APP gene sequence is upstream of IRES2-GFP sequence. IRES2 sequence allows bicistronic expression of APP and GFP under a neuron-specific promoter, synapsin. It has been indicated that transduced cells with a variety of bicistronic LV strongly express upstream gene of IRES sequence, whereas GFP expression (downstream gene of IRES sequence) is very low or undetectable in these cells	31233762	Details
RORC	IFN-b-1a	inhibitor	MS	N/A	Findings indicate that IFN-b-1a suppresses Th22 and Th17 cell responses, which were associated with decreased MRI-detectable demyelination	IFN-b-1a induced reductions in transcription factor AHR, T-bet, and retinoic acid–related orphan nuclear hormone receptor C (RORc) gene expression, while it increased GATA3’s expression in CD41 cells	26601116	Details
AKT1	LXW7	inhibitor	chronic neurodegenerative diseases (e.g., Alzheimer′s disease, Parkinson′s disease, multiple sclerosis, amyotrophic lateral sclerosis)	BV2 microglial cell	The anti-inflammatory effects of LXW7 may be associated with the inhibition of microglial activation via Akt/NF-κB and JNK/MAPK signaling pathways by blocking integrin αvβ3 receptor. The present study′s findings suggest that LXW7 has a substantial therapeutic potential for treating inflammatory and neurodegenerative diseases.	Akt/NF-κB and JNK/MAPK signaling pathways by blocking integrin αvβ3 receptor	31732449	Details
Gpr173	Phoenixin-14	inhibitor	MS	C57BL/6 mice	we demonstrate that PNX-14 could attenuate LPS-induced ER stress response and NLRP3 infammasome activation in mouse cerebral astrocytes	Phoenixin-14 (PNX-14) is a ligand for the G protein-coupled receptor GPR173, which we demonstrate to be expressed in astrocytes and suppressed by exposure to lipopolysaccharide (LPS). Endoplasmic reticulum (ER) stress resulting from injury or disease leads to the unfolded protein response, which is mediated by the activation of transcription factors including eIF-2α, ATF4, and CHOP, and regulated by GADD34. ER stress also leads to a robust neuroinfammatory response, which is mediated by HMGB1-induced activation of the NLRP3 infammasome and subsequent production of IL-1β and IL-18	32435966	Details
CCL5	Glatiramer acetate	inhibitor	MS	brain	glatiramer acetate may exert its therapeutic effect in MS partially through inhibiting NF-kB activation and chemokine production	our electrophoretic mobility shift assays of nuclear extracts from TNF-a-treated cells reveal an increase in DNA-binding activity specic for the nuclear factor-kappa B (NF-kB) binding site, in the 50 -ˉanking promoter region of the human RANTES gene, and that this increase in NF-kB binding activity is prevented by pretreatment with glatiramer acetate or the NF-kB inhibitors.	11389171	Details
Nos2	N-[3,4-Dimethoxycinnamoyl]-anthranilic acid (tranilast, TNL)	inhibitor	MS	brain	In summary, we show that TNL inhibits LPS-induced activation of iNOS by inhibiting the activation of PKCd and ERK-2, thus possibly affecting post-translational modification of iNOS mRNA. Our result may have further implications for the use of TNL as a novel therapeutic agent in neurological disorders associated with activation of microglia and increased NO release, including multiple sclerosis	PKCd and ERK-2	14505805	Details
IL2	Clofazimine	activator	MS	Peripheral blood	clofazimine is a promising immunomodulatory drug candidate for treating a variety of autoimmune disorders.	Clofazimine was initially identified as an inhibitor of intracellular T cell receptor-mediated signaling leading to the transcriptional activation of human interleukin-2 gene in T cells from a screen of the Johns Hopkins Drug Library. A systematic mechanistic deconvolution revealed that clofazimine selectively blocked the Kv1.3 channel activity, perturbing the oscillation frequency of the calcium-release activated calcium channel, which in turn led to the inhibition of the calcineurin-NFAT signaling pathway.	19104661	Details
Nos2	kalopanaxsaponin A	inhibitor	inflammatory effects	microglia	we showed that kalopanaxsaponin A, a triterpenoid saponin isolated from Kalopanax pictus, inhibited inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and tumor necrosis factor (TNF)-α expression in lipopolysaccharide (LPS)-stimulated microglia, while kalopanaxsaponin A increased anti-infl ammatory cytokine interleukin (IL)-10 expression. Subsequent mechanistic studies revealed that kalopanaxsaponin A inhibited LPS-induced DNA binding activities of NF-κB and AP-1, and the phosphorylation of JNK without affecting other MAP kinases. Furthermore, kalopanaxsaponin A inhibited the intracellular ROS production with upregulation of anti-infl ammatory hemeoxygenase-1 (HO-1) expression. Based on the previous reports that JNK pathway is largely involved in iNOS and proinfl ammatory cytokine gene expression via modulating NF-κB/AP-1 and ROS, our data collectively suggest that inhibition of JNK pathway plays a key role in anti-infl ammatory effects of kalopanaxsaponin A in LPS-stimulated microglia	JNK pathway is largely involved in iNOS and proinfl ammatory cytokine gene expression via modulating NF-κB/AP-1 and ROS	24244819	Details
ERVW-1	AgNPs	inhibitor	leukaemia and multiple sclerosis	Peripheral blood	AgNPs induce syncytin-1 expression in leukaemic cell lines	FA-AML1 cells were more sensitive overall than MOLT-4 to treatment with the smaller 7nm sized AgNp’s being the most toxic in these cells	27576335	Details
IL1B	Glatiramer	inhibitor	MS	Peripheral blood	These results suggest that glatiramer acetate might alter macrophage effector function and suggest that further studies in human monocytes and macrophages are warranted	glatiramer acetate on the human monocytic cell line, THP-1, activated by lipopolysaccharide and interferon-g as a model for macrophages	9548401	Details
Tgfb1	TGF-b1	inhibitor	EAE	Peripheral blood	TGF-b1 gene delivery had pronounced downregulatory effects on T cell proliferation and production of interferon c (IFN-c ) and tumor necrosis factor a (TNF-a), on in vitro restimulation with MBP. IL-4-IgG1 vector administration also suppressed these responses, although much less than TGF-b1, and enhanced secretion of endogenous IL-4. Therapy resulted in a significant decrease in the severity of histopathologic inflammatory lesions. In the CNS, treatment with either vector suppressed IL-12 and IFN-c mRNA expression, while IL-4 and TGF-b1 mRNA levels were increased compared with control mice. Thus, cytokine plasmid treatment appeared to inhibit MBP-specific pathogenic Th1 responses, while enhancing endogenous secretion of protective cytokines. We demonstrate that gene therapy with these vectors is an effective therapeutic strategy for EAE	We studied the immunoregulatory properties of TGF-b1 and IL-4 in an animal model of EAE, by direct intramusculas injection of plasmid DNA expression vectors encoding either TGF-b1 (pVR-TGF-b1) or an IL-4–IgG1 chimeric protein (pVR-IL-4-IgG1). Treatment with either vector resulted in cytokine production capable of suppressing CNS inflammation in mice with MBP-induced EAE. Both cytokines had downregulatory effects on T cell proliferation, and production of proinflammatory cytokines, although TGF-b1 was more suppressive. As well, cytokine gene therapy enhanced the production of endogenous regulatory cytokines in lymph node cells and CNS tissue. Somatic cytokine gene therapy proved to be effective in this autoim- mune disease.	10466625	Details
Mbp	TGF-b1	inhibitor	EAE	Peripheral blood	TGF-b1 gene delivery had pronounced downregulatory effects on T cell proliferation and production of interferon c (IFN-c ) and tumor necrosis factor a (TNF-a), on in vitro restimulation with MBP. IL-4-IgG1 vector administration also suppressed these responses, although much less than TGF-b1, and enhanced secretion of endogenous IL-4. Therapy resulted in a significant decrease in the severity of histopathologic inflammatory lesions. In the CNS, treatment with either vector suppressed IL-12 and IFN-c mRNA expression, while IL-4 and TGF-b1 mRNA levels were increased compared with control mice. Thus, cytokine plasmid treatment appeared to inhibit MBP-specific pathogenic Th1 responses, while enhancing endogenous secretion of protective cytokines. We demonstrate that gene therapy with these vectors is an effective therapeutic strategy for EAE	We studied the immunoregulatory properties of TGF-b1 and IL-4 in an animal model of EAE, by direct intramusculas injection of plasmid DNA expression vectors encoding either TGF-b1 (pVR-TGF-b1) or an IL-4–IgG1 chimeric protein (pVR-IL-4-IgG1). Treatment with either vector resulted in cytokine production capable of suppressing CNS inflammation in mice with MBP-induced EAE. Both cytokines had downregulatory effects on T cell proliferation, and production of proinflammatory cytokines, although TGF-b1 was more suppressive. As well, cytokine gene therapy enhanced the production of endogenous regulatory cytokines in lymph node cells and CNS tissue. Somatic cytokine gene therapy proved to be effective in this autoim- mune disease.	10466625	Details
Trav6-3	OVA	inhibitor	EAE	splenocytes	we conclude that CD41 T regulatory cells do not express canonical TCRs and that the altered signaling properties brought about by coexpression of two TCRs are not sufficient for the generation of regulatory T cells. Instead, our results indicate that regulatory T cells belong to a population displaying wide TCR diversity, but in which TCR specificity is central to their protective function	as myelin basic protein-specific/OVA-specific recombinase activating gene-12/2 double TCR transgenic mice still developed experimental autoimmune encephalomyelitis spontaneously even after immunization with OVA	10799918	Details
Cxcl10	IFN	inhibitor	EAE	brain、spleen、thymus	CXCL10 produced in the LN plays a specific inhibitory role in the development of Th1-mediated diseases such as EAE by holding sensitized and activated Th1s expressing CXCR3 in the draining LN	Induction of gene expression of CXCL9/Mig and CXCL10 and their receptor CXCR3 was confirmed in the draining LN in EAE rats	12115662	Details
Cxcr3	IFN	inhibitor	EAE	brain、spleen、thymus	CXCL10 produced in the LN plays a specific inhibitory role in the development of Th1-mediated diseases such as EAE by holding sensitized and activated Th1s expressing CXCR3 in the draining LN	Induction of gene expression of CXCL9/Mig and CXCL10 and their receptor CXCR3 was confirmed in the draining LN in EAE rats	12115662	Details
CCR5	Natalizumab	inhibitor	MS	mononuclear cells (PBMCs) and CSF surface cell molecules	Natalizumab treatment alters the percentage of CCR5+ and CD4+ cells in CSF. In view of the excellent temporary clinical results of the therapy, which are yet to be assessed in the course of a longer time period, our results show a possible explanation for the therapeutic success of this drug as well as for the development of progressive multifocal leukoencephalopathy	CD4+ autoreactive T cells and their differentiation into Th1 phenotype are crucial events in the initial phases	17911462	Details
IFIH1	IFN-β 1a	inhibitor	MS	Peripheral blood	Thus, it seems that IFN-β 1a not only decreased pathogenic inflammatory responses but also modulated the expression of RIG-1 to protect the patients from infectious diseases and upregulation of IFN-I in a positive feedback	Melanoma differentiation-associated protein 5 (MDA5) and retinoic acid-inducible gene 1 (RIG-1) are two critical pathogen recognition receptors (PRRs), which detect intracytoplasmic intracellular dsRNA [10–13]. MDA5 and RIG-1 use the same pathway; they both use interferon promoter stimulator 1 (IPS1) to activate two important transcription factors including interferon regulatory transcription factor 3 (IRF3) and nuclear factor-kappa B (NF-κB)	32311159	Details
RIGI	IFN-β 1a	inhibitor	MS	Peripheral blood	Thus, it seems that IFN-β 1a not only decreased pathogenic inflammatory responses but also modulated the expression of RIG-1 to protect the patients from infectious diseases and upregulation of IFN-I in a positive feedback	Melanoma differentiation-associated protein 5 (MDA5) and retinoic acid-inducible gene 1 (RIG-1) are two critical pathogen recognition receptors (PRRs), which detect intracytoplasmic intracellular dsRNA [10–13]. MDA5 and RIG-1 use the same pathway; they both use interferon promoter stimulator 1 (IPS1) to activate two important transcription factors including interferon regulatory transcription factor 3 (IRF3) and nuclear factor-kappa B (NF-κB)	32311159	Details
CNTF	AD4	activator	MS	spinal cords	In conclusion, our current study demonstrates that chronic administration of AD4 preserved the healthy gene expression of MOG-induced EAE mice.	N/A	16055951	Details
Ifnk	pMxkIFNkβ	inhibitor	MS	spinal cords	These results indicate that IFNkβ transgene expression by single administration of the pMxkIFNkβ can be an effective longkterm treatment for MS	Gene transfer of pMxcIFNcβ reduced the severity of EAE. The EAE mice received a single administration of plasmid DNA by hydrodynamic injection on day 7 after the initial immunization with MOG35k55. pMxkgLuc, a plasmid vector encoding the reporter protein gLuc, was used as control vector.	28257578	Details
Foxp3	MOG	activator	MS	splenocytes	We demonstrate that mice treated prophylactically are protected from developing disease and neurological deficits. More importantly, we demonstrate that when given to mice with preexisting disease, ranging from mild neurological deficits to severe paralysis, the gene immunotherapy abrogated CNS inflammation and significantly reversed clinical symptoms of disease.	We show that by harnessing the tolerogenic nature of the liver, this powerful gene immunotherapy restores immune tolerance by inducing functional MOG-specific regulatory T cells (Tregs) in vivo, independent of major histocompatibility complex (MHC) restrictions	28943274	Details
Ifnb1	gal-9	activator	MS	peripheral blood	These results indicate that gene therapy using IFN-β-gal-9 fusion proteins is expected to be safe and effective for the treatment of MS	The IFN-β-gal-9 fusion proteins showed less IFN-β biological activity on non-T cells than IFN-β alone	29217470	Details
Ifnb1	LEV	activator	EAE	peripheral blood	In summary, LEV showed only minor anti-inflammatory effects not sufficient to ameliorate disease course in an autoimmune inflammatory disease of CNS	anti-inflammatory properties via modulation of interleukin (IL)-1β and transforming-growth-factor (TGF)-β1	22691576	Details
Ifna1	B18R	activator	EAE	peripheral blood、peritoneal	The mimetics lack toxic side effects of the parent IFNs and, thus, are a potent therapeutic replacement of IFNs as therapeutics	human IFNa1(152–189), human IFNb(150–187), and ovine IFNt(156–195) are derived from the C-terminus of the parent IFNs and function intracellularly based on the noncanonical model	24811478	Details
Ppara	retinoid	activator	MS	peripheral blood	Pharmacologic activation of PPARr prevented removal of the silencing mediator for retinoid and thyroid hormone receptors corepressor from the RORrt promoter in T cells, thus interfering with RORrt transcription	Control of Th17 differentiation by PPARr involved inhibition of TGF-r/IL-6–induced expression of RORrt in T cells	19737866	Details