Nature Immunology:非編碼小RNA在多發性硬化症發生過程中作用機制

作為一類病因複雜且缺乏有效治療手段的中樞神經系統自身免疫疾病，多發性硬化症多年來一直困擾著國際醫療界。我國科學家最新的一項研究揭示了非編碼小RNA在多發性硬化症發生過程中的新機制。

由中國科學院上海生命科學研究院生物化學與細胞生物學研究所裴鋼院士領導的研究組及他們的合作者，在研究中發現一種非編碼小RNA (miR-326)在多發性硬化症病人的CD4+T細胞亞群中特異性上調。而近年來免疫學家發現，人體中的CD4+T細胞亞群的大量誘導及其對病灶部位的主動入侵，能加速誘發組織損傷。

研究人員通過多發性硬化症的小鼠模型研究進一步證實，人為提高非編碼小RNA (miR-326)的水平，會加重小鼠的病情，而抑制非編碼小RNA (miR-326)的水平，則能顯著減輕小鼠的病情。

這一研究成果已於10月19日在線發表在國際著名學術期刊《自然·免疫》網絡版上。業內專家認為，該項研究不僅揭示了非編碼小RNA在多發性硬化症發生過程中的新機制，並且為包括多發性硬化症在內的自身免疫疾病的治療，提供了可借鑑的新策略。

我國科學家進行的這項研究，得到了科技部、國家自然科學基金、上海市科委和中國科學院的資金資助，相關研究成果已申請專利。（生物谷Bioon.com）

裴剛院士近期研究成果：

Nature：胰島素耐受/II型糖尿病發病機制研究

生物谷推薦原始出處：

Nature Immunology 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

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.

1 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.
2 School of Life Science and Technology, Tongji University, Shanghai, China.
3 Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Shanghai, China.
4 Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
5 These authors contributed equally to this work.