MicroRNA miR-326 regulates TH-17 differentiation and is associated with the pathogenesis of multiple sclerosis
MicroRNA miR-326 regulates TH-17 differentiation and is associated with the pathogenesis of multiple sclerosis
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DOI：
10.1038/ni.1798
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发表时间：
2009-12-01
影响因子：
30.5
通讯作者：
Pei, Gang
中科院分区：
文献类型：
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作者：
Du, Changsheng;Liu, Chang;Pei, Gang
产生白细胞介素17（IL-17）的T辅助细胞（T-H-17细胞）越来越被认为是各种自身免疫性疾病（包括多发性硬化症）的关键参与者。尽管已知转录因子和细胞因子集调节T-H-17分化，但对非编码RNA的作用知之甚少。在这里，我们确定了T-H-17细胞相关的microRNA，miR-326，其表达与多发性硬化症患者和实验性自身免疫性脑脊髓炎（EAE）小鼠的疾病严重程度高度相关。体内沉默miR-326导致较少的T-H-17细胞和轻度EAE，而其过表达导致更多的T-H-17细胞和严重的EAE。我们还发现miR-326通过靶向Ets-1（T-H-17分化的负调节因子）促进T-H-17分化。我们的数据显示microRNA在T-H-17分化和多发性硬化症发病机制中的关键作用。
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.