MicroRNA miR-326 regulates TH-17 differentiation and is associated with the pathogenesis of multiple sclerosis

• DOI: 10.1038/ni.1798
• Publication Date: 2009-10-18T19:07:01Z
• Authors: Changsheng Du; Chang Liu; Jiuhong Kang; Guixian Zhao; Zhiqiang Ye; Shichao Huang; Zhenxin Li; Zhiying Wu; Gang Pei
• Keywords: Adult; Male; Encephalomyelitis, Autoimmune, Experimental; Multiple Sclerosis; Base Sequence; Interleukin-17; Cell Differentiation; T-Lymphocytes, Helper-Inducer; Up-Regulation; Proto-Oncogene Protein c-ets-1; Mice; MicroRNAs; Animals; Humans; Female

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.