DNA Methylation: a New Player in Multiple Sclerosis.
Multiple sclerosis (MS) is a neurological and chronic inflammatory disease that is mediated by demyelination and axonal degeneration in the central nervous system (CNS). Studies have shown that immune system components such as CD4+, CD8+, CD44+ T cells, B lymphatic cells, and inflammatory cytokines play a critical role in inflammatory processes and myelin damage associated with MS. Nevertheless, the pathogenesis of MS remains poorly defined. DNA methylation, a significant epigenetic modification, is reported to be extensively involved in MS pathogenesis through the regulation of gene expression. This review focuses on DNA methylation involved in MS pathogenesis. Evidence showed the hypermethylation of human leukocyte antigen-DRB1 (HLA-DRB1) in CD4+ T cells, the genome-wide DNA methylation in CD8+ T cells, the hypermethylation of interleukin-4 (IL-4)/forkhead winged helix transcription factor 3 (Foxp3), and the demethylation of interferon-γ (IFN-γ)/IL-17a in CD44+ encephalitogenic T cells. Studies also showed the hypermethylation of SH2-containing protein tyrosine phosphatase-1 (SHP-1) in peripheral blood mononuclear cells (PBMCs) and methylated changes of genes regulating oligodendrocyte and neuronal function in normal-appearing white matter. Clarifying the mechanism of aberrant methylation on MS may explain part of the pathology and will lead to the development of a new therapeutic target for the treatment of MS in the future.
Department of Histology and Embryology, Faculty of Basic Medicine, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, No. 30 Gaotanyan Street, Chongqing, 400038, China.|The Thirteenth Camp of Cadet Brigade, Third Military Medical University, No. 30 Gaotanyan Street, Chongqing, 400038, China.
Xiang
X
Li
Department of Histology and Embryology, Faculty of Basic Medicine, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, No. 30 Gaotanyan Street, Chongqing, 400038, China.|The Eleventh Camp of Cadet Brigade, Third Military Medical University, No. 30 Gaotanyan Street, Chongqing, 400038, China.
Bing
B
Xiao
Department of Histology and Embryology, Faculty of Basic Medicine, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, No. 30 Gaotanyan Street, Chongqing, 400038, China. xingshuchen2011@163.com.
Xing-Shu
XS
Chen
D000818:Animals; D019175:DNA Methylation / Q000235:genetics*; D016678:Genome; D006801:Humans; D009103:Multiple Sclerosis / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D009474:Neurons / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D066127:White Matter / Q000473:pathology
DNA methylation; Epigenetics; Multiple sclerosis