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 O-linked N-acetylglucosamine transferase is a potential target of miR-15b, enabling it to affect the transcriptional regulation of retinoic acid–related orphan receptor γT through O-linked N-acetylglucosamine glycosylation of NF-κB. These results contribute to the importance of miR-15b in Th17 differentiation and the pathogenesis of MS.
This work was supported by National Natural Science Foundation of China Grants 81571600, 81322018, 81273287, and 81100887 (to J.H.), 81322032 and 81472733 (to Y.W.), and 81401361 (to X.M.), Ministry of Education of China Grants NCET-12-1067, FANEDD-201231, and RFDP-20131202110012 (to Y.W.), and by grants from the Youth Top-Notch Talent Support Program (to J.H.) and from the National Key Clinical Specialty Construction Project of China (to J.H.).
The online version of this article contains supplemental material.
Abbreviations used in this article:
- chromatin immunoprecipitation
- draining lymph node
- experimental autoimmune encephalomyelitis
- myelin oligodendrocyte glycoprotein
- magnetic resonance imaging
- multiple sclerosis
- O-linked N-acetylglucosamine
- O-GlcNAc glycosylation
- retinoic acid–related orphan receptor
- relapsing/remitting multiple sclerosis
- regulatory T cell
- untranslated region
- Received October 6, 2016.
- Accepted January 30, 2017.
- Copyright © 2017 by The American Association of Immunologists, Inc.