Article abstract
Nature Immunology 10, 1252 - 1259 (2009)
Published online: 18 October 2009 | doi:10.1038/ni.1798
MicroRNA miR-326 regulates TH-17 differentiation and is associated with the pathogenesis of multiple sclerosis
Changsheng Du1,5, Chang Liu1,5, Jiuhong Kang1,2, Guixian Zhao3, Zhiqiang Ye4, Shichao Huang1, Zhenxin Li3, Zhiying Wu3 & Gang Pei1,2
Abstract
Interleukin 17 (IL-17)-producing T helper cells (TH-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 TH-17 differentiation, the role of noncoding RNA is poorly understood. Here we identify a TH-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 TH-17 cells and mild EAE, and its overexpression led to more TH-17 cells and severe EAE. We also found that miR-326 promoted TH-17 differentiation by targeting Ets-1, a negative regulator of TH-17 differentiation. Our data show a critical role for microRNA in TH-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.
- School of Life Science and Technology, Tongji University, Shanghai, China.
- Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Shanghai, China.
- Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
- These authors contributed equally to this work.
Correspondence to: Gang Pei1,2 e-mail: gpei@sibs.ac.cn
