当前位置： SCI文献检索 > INTERNATIONAL IMMUNOPHARMACOLOGY期刊下所有文献 > miR-140-5p regulates T cell differentiation and attenuates experimental autoimmune encephalomyelitis by affecting CD4+T cell metabolism and DNA methylation.

miR-140-5p regulates T cell differentiation and attenuates experimental autoimmune encephalomyelitis by affecting CD4+T cell metabolism and DNA methylation.

Abstract：

:We previously demonstrated that decreased expression of miR-140-5p was associated with the progression of multiple sclerosis (MS) and miR-140-5p targeted STAT1 and interfered with the expression of IFN-γ. However, the underlying mechanisms how miR-140-5p regulated the differentiation of encephalomyelitic CD4+T cell remained unclear. In this study, we analyzed the levels of miR-140-5p in a mouse model of experimental autoimmune encephalomyelitis (EAE). We also analyzed the outcomes in response to either over- or under-expression of miR-140-5p. We found that the expression of miR-140-5p was inversely related to the progression of EAE. With the remission of the disease, the expression of miR-140-5p was restored to levels comparable to the control. The expression of miR-140-5p was downregulated in the encephalomyelitic CD4+T cells whereas enhanced expression of miR-140-5p inhibited the development of T helper type 1 (Th1) cell and significantly attenuated EAE. MiR-140-5p also caused hypermethylation of STAT1 and demethylation of GATA3. Furthermore, we found that miR-140-5p enhanced mitochondrial glycolysis in CD4+T cells with simultaneous activation of ATP activity. By blockage of the respiratory electron transport chain with the inhibitors of complex I and III, the effect of miR-140-5p on Th1 differentiation was blocked, which suggested a role for mitochondrial respiratory pathway in miR-140-5p-mediated inhibition of Th1 differentiation. In summary, our results demonstrated that the expression of miR-140-5p was negatively correlated with the progression of EAE and that miR-140-5p regulated Th1 differentiation via DNA methylation and mitochondrial respiratory pathway.

journal_name

Int Immunopharmacol

journal_title

International immunopharmacology

authors

Zhu S,Zhang X,Guan H,Huang F,Wu L,Hou D,Zheng Z,Yu M,Huang L,Ge L

doi

10.1016/j.intimp.2019.105778

subject

Has Abstract

pub_date

2019-10-01 00:00:00

pages

105778

eissn

1567-5769

issn

1878-1705

pii

S1567-5769(19)30926-9

journal_volume

pub_type

杂志文章

在线工具

miR-140-5p regulates T cell differentiation and attenuates experimental autoimmune encephalomyelitis by affecting CD4+T cell metabolism and DNA methylation.