M6A methylation modification in autoimmune diseases, a promising treatment strategy based on epigenetics

Huang, Yurong; Xue, Qiuyun; Chang, Jun; Wang, Yuting; Cheng, Chenglong; Xu, Suowen; Wang, Xiao; Miao, Chenggui

doi:10.1186/s13075-023-03149-w

Arthritis Research & Therapy

Table 3 Regulators associated with M6A methylation in autoimmune diseases

From: M6A methylation modification in autoimmune diseases, a promising treatment strategy based on epigenetics

Disease	The m6A regulators	Type	Sample source	Expression change	Regulatory roles	Reference
RA	IGFBP2	Reader	FLS	Up-regulation	Regulates the neuropeptides GHR and NPR2 to influence the interaction between FLS.	[37]
RA	IGF2BP3	Reader	Synovial tissues	Up-regulation	Regulates the G2/M transition and affects the polarization of M1 macrophages.	[38]
RA	SMOC2	-	Synovial tissues	Up-regulation	Controls MYO1C expression through ALKBH5-mediated m6A modification.	[40]
RA	METTL3	Writer	PBMC	Up-regulation	Attenuated LPS-induced inflammatory response in macrophages via the NF-κB signaling pathway.	[41]
RA	METTL3	Writer	FLS	Up-regulation	Activates the NF-κB signaling pathway.	[43]
RA	WTAP	Writer	MH7A cells	Up-regulation	Combines with METTL3 to form the MettL3–MettL14–Wtap complex.	[52]
RA	RIPK2	-	MH7A cells	Up-regulation	Mediates LPS-induced p38 and IKB-α signaling.	[52]
RA	JAK3	-	MH7A cells	Up-regulation	Mediates and participates in the formation of cytokines.	[52]
RA	TNFRSF10A	-	MH7A cells	Down-regulation	Activates the NF-κB pathway and promotes cell proliferation and migration.	[52]
RA	YTHDF2	Reader	PBMC	Down-regulation	Affects the production of autoantibodies.	[53]
RA	FTO	Eraser	Peripheral blood	Down-regulation	Mediates methylation reversal.	[53]
RA	ALKBH	Eraser	Peripheral blood	Down-regulation	Mediates methylation reversal.	[53]
SLE	ALKBH5	Eraser	Peripheral blood	Down-regulation	Affects anti-DSDNA levels	[63]
SLE	MTEEL14	Writer	Peripheral blood	Down-regulation	Perturbs the m6A threshold, leading to uncontrolled expression/activity of the virulence gene.	[64]
SLE	YTHDF2	Reader	Peripheral blood	Down-regulation	Perturbs the m6A threshold, leading to uncontrolled expression/activity of the virulence gene.	[64]
pSS	METTL3 FTO YTHDF1 YTHDF2	Writer Eraser Reader Reader	PBMC	Up-regulation	Targets ISG15, stimulates ISG15 expression, and activates the type I IFN signaling pathway.	[72]
Graves’Disease	METTL3	Writer	CD4T cells	Down-regulation	Induces SOCS mRNA m6A modification.	[79]
MS	ALKBH5	Eraser	T cells	Up-regulation	Controls CD4 T cell pathogenicity.	[89]
Uveitis	FTO	Eraser	EAU mouse RPE cells	Down-regulation	Regulates the m6A level of ATF4 to affect the translation of ATF4 and the expression of inflammatory factors.	[92]
Autoimmune hepatitis	YTHDF2	Reader	liver	Up-regulation	Low expression of YTHDF2 can enhance the amplification, chemotaxis, and inhibition of MDSC.	[96]

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ISSN: 1478-6362

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