MicroRNA miR-326 regulates TH-17 differentiation and is associated with the pathogenesis of multiple sclerosis.
Interleukin 17 (IL-17)-producing T helper cells (T(H)-17 cells) are increasingly recognized as key participants in various autoimmune diseases, including multiple sclerosis. Although sets of transcription factors and cytokines are known to regulate T(H)-17 differentiation, the role of noncoding RNA is poorly understood. Here we identify a T(H)-17 cell-associated microRNA, miR-326, whose expression was highly correlated with disease severity in patients with multiple sclerosis and mice with experimental autoimmune encephalomyelitis (EAE). In vivo silencing of miR-326 resulted in fewer T(H)-17 cells and mild EAE, and its overexpression led to more T(H)-17 cells and severe EAE. We also found that miR-326 promoted T(H)-17 differentiation by targeting Ets-1, a negative regulator of T(H)-17 differentiation. Our data show a critical role for microRNA in T(H)-17 differentiation and the pathogenesis of multiple sclerosis.
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Changsheng
C
Du
Chang
C
Liu
Jiuhong
J
Kang
Guixian
G
Zhao
Zhiqiang
Z
Ye
Shichao
S
Huang
Zhenxin
Z
Li
Zhiying
Z
Wu
Gang
G
Pei
D000328:Adult; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009103:Multiple Sclerosis / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation
C494042:Ets1 protein, mouse; D020381:Interleukin-17; C545322:MIRN326 microRNA, human; C545323:MIRN326 microRNA, mouse; D035683:MicroRNAs; D050784:Proto-Oncogene Protein c-ets-1