MicroRNA-15b Suppresses Th17 Differentiation and Is Associated with Pathogenesis of Multiple Sclerosis by Targeting O -GlcNAc Transferase

• Published in: The Journal of immunology (1950) 2017-04, Vol.198 (7), p.2626-2639
• Main Authors: Liu, Ruiqiong, Ma, Xiaofeng, Chen, Li, Yang, Yang, Zeng, Yi, Gao, Jie, Jiang, Wei, Zhang, Fang, Li, Daojing, Han, Bin, Han, Ranran, Qiu, Rongfang, Huang, Wei, Wang, Yan, Hao, Junwei
• Format: Article
• Language: English
• Subjects: Animals; Autoimmune diseases; Blotting, Western; Cell Differentiation - genetics; Cell Differentiation - immunology; Cell Separation; Down-Regulation; Encephalomyelitis, Autoimmune, Experimental - genetics; Encephalomyelitis, Autoimmune, Experimental - immunology; Experimental allergic encephalomyelitis; Flow Cytometry; Gene Expression Regulation - immunology; Gene Knockdown Techniques; Gene regulation; Glycosylation; Helper cells; Humans; Immunoprecipitation; Interleukin 17; Lymphocytes T; Mice; Mice, Inbred C57BL; MicroRNAs; MicroRNAs - genetics; MicroRNAs - immunology; miRNA; Multiple sclerosis; Multiple Sclerosis - genetics; Multiple Sclerosis - immunology; N-Acetylglucosamine; N-Acetylglucosaminyltransferases - biosynthesis; N-Acetylglucosaminyltransferases - immunology; NF-κB protein; Pathogenesis; Real-Time Polymerase Chain Reaction; Retinoic acid; Rodents; Th17 Cells - immunology; Transcription
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1601727

IL-17-producing Th17 cells have gradually become considered as key factors in the pathogenesis of many autoimmune diseases, including multiple sclerosis (MS). Although the involvement of certain microRNAs in the development of MS has been reported, their role in Th17-driven autoimmunity is still poorly understood. In this study, we identified microRNA (miR)-15b as an important factor in Th17-associated effects and determined that the expression of miR-15b is significantly downregulated in MS patients and in mice with experimental autoimmune encephalomyelitis. Overexpression of miR-15b alleviated experimental autoimmune encephalomyelitis, whereas knockdown of miR-15b aggravated it. We demonstrated that miR-15b suppressed Th17 differentiation both in vivo and in vitro. We also found that -linked  -acetylglucosamine transferase is a potential target of miR-15b, enabling it to affect the transcriptional regulation of retinoic acid-related orphan receptor γT through -linked  -acetylglucosamine glycosylation of NF-κB. These results contribute to the importance of miR-15b in Th17 differentiation and the pathogenesis of MS.