miR26a Modulates Th17/Treg Balance in the EAE Model of Multiple Sclerosis by Targeting IL6

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• 作者：Rongwei Zhang (1)
  Ayong Tian (2)
  Jun Wang (3)
  Xueli Shen (1)
  Guoxian Qi (1)
  Yanqing Tang (1)
  
  1. Department of Gerontology and Geriatrics ; The First Affiliated Hospital of China Medical University ; No. 155 ; Nanjing North Street ; Heping District ; Shenyang ; 110001 ; Liaoning ; China
  2. Department of Anesthesiology ; The First Affiliated Hospital of China Medical University ; Shenyang ; China
  3. Department of Neurology ; The First Affiliated Hospital of China Medical University ; Shenyang ; China
  
• 关键词：Multiple sclerosis ; Experimental autoimmune encephalomyelitis ; miR26a ; Th17 ; Treg ; IL6
• 刊名：NeuroMolecular Medicine
• 出版年：2015
• 出版时间：March 2015
• 年：2015
• 卷：17
• 期：1
• 页码：24-34
• 全文大小：3,827 KB
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• 刊物主题：Neurosciences; Neurology; Internal Medicine;
• 出版者：Springer US
• ISSN：1559-1174

文摘

A number of different microRNAs (miRNAs) have been implicated in various autoimmune diseases, including multiple sclerosis (MS). T helper (Th)17 and regulatory T cells (Tregs) have likewise been implicated as key players in MS, and a functional imbalance of these cell types is increasingly recognized as a key etiological factor in the disease. Although specific panels of transcription factors and cytokines are known to regulate the Th17/Treg balance, the role of noncoding RNAs remains poorly understood. The inflammatory cytokine, interleukin (IL)6, appears to play a critical role in both the development of the Th17 response and the inhibition of Treg functions. In this research, an IL6-associated miRNA, miR26a, was identified, and its normally downregulated expression was shown to be highly correlated with disease severity in patients suffering from MS as well as in C57BL/6 mice with experimental autoimmune encephalomyelitis (EAE; a well-established animal model of human MS). Using the EAE model system, in vivo silencing of miR26a was found to result in increased expression of Th17-related cytokines and increased severity of EAE, while overexpression of miR26a was found to result in reduced expression of Th17-related cytokines and a milder form of EAE. By contrast, Treg cell-specific transcription factor, Foxp3, was found to be positively correlated with miR26a expression. Finally, miR26a was found to downregulate Th17 and to upregulate Treg cell function through its targeting of IL6. Taken together, our data indicate an important role for miR26a in maintaining the Th17 and Treg cell balance in MS that involves repression of IL6 expression.