miR-20b suppresses Th17 differentiation and the pathogenesis of experimental autoimmune encephalomyelitis by targeting RORγt and STAT3.
The differentiation and function of IL-17-producing Th17 cells are tightly regulated by specific transcription factors and cytokines, which are the key participants in the pathogenesis of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). Although specific miRNAs have been shown to be involved in the development of MS and EAE, the potential role of miRNAs in the context of Th17-driven autoimmunity is just beginning to be clarified. miR-20b has been reported as a downregulated miRNA in blood cells of MS patients. In this report, it was further studied in greater detail because we found it was significantly downregulated during EAE, and, in the in vitro differentiation model, Th17 cells had lower expression of miR-20b than did Th1, Th2, or inducible T regulatory cells. Ectopic expression of miR-20b repressed Th17 differentiation in vitro. Using lentiviral vectors for miR-20b overexpression in vivo, we demonstrated that overexpression of miR-20b led to decreased Th17 cells and reduced severity of EAE. Furthermore, we also identified both RAR-related orphan receptor γt and STAT3 as potential targets of miR-20b. Finally, we confirmed that the mild disease severity and low number of Th17 cells in LV-miR-20b-infected mice were largely reversed by coinfection of these mice with lentivirus-expressing RAR-related orphan receptor γt or STAT3 3'-untranslated regions. Taken together, our results contribute to the importance of miRNAs in Th17 differentiation and pathogenesis of MS and EAE.
State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China; and.
Endong
E
Zhu
State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China; and.
Xi
X
Wang
State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China; and.
Bin
B
Zheng
State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China; and.
Qian
Q
Wang
State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China; and.
Jianlei
J
Hao
State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China; and.
Siming
S
Chen
Department of Zoology and Developmental Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.
Qiang
Q
Zhao
State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China; and.
Liqing
L
Zhao
State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China; and yinzn@nankai.edu.cn naturepower@nankai.edu.cn.
Zhenzhou
Z
Wu
State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China; and yinzn@nankai.edu.cn naturepower@nankai.edu.cn.
Zhinan
Z
Yin
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology*; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000276:immunology*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology
D035683:MicroRNAs; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse