title: MiR-30a inhibits Th17 differentiation and demyelination of EAE mice by targeting the IL-21R.
abstract: T helper cells 17 (Th17) are recognized as key participants in the pathogenesis of chronic autoimmune diseases such as multiple sclerosis (MS). Regulation of Th17 differentiation is a valuable strategy for diagnosis and treatment of these complicated immune disorders. Here, by genome-wide expression profiling of microRNAs (miRs), we screened miR-30a, whose level was greatly decreased during Th17 differentiation and the process of demyelination disease, both in MS patients and experimental autoimmune encephalomyelitis (EAE) mice. Enforced constitutive expression of miR-30a in naïve T cells inhibited their differentiation into Th17, and in vivo overexpression of miR-30a resulted in fewer Th17 and alleviative EAE. Moreover, target prediction analysis and dual luciferase report assay revealed that interleukin-21 receptor (IL-21R) was a direct target of miR-30a, a finding consistent with the results that miR-30a downregulated the expression of IL-21R, while overexpression of IL-21R alleviated the inhibitory effect of miR-30a on Th17 differentiation. Taken together, our findings imply that miR-30a inhibits Th17 differentiation and the pathogenesis of MS by targeting IL-21R.
authors.affiliation: Department of Neurobiology, Xuzhou Medical College, Xuzhou 221004, Jiangsu, China.
authors.forename: Xuebin
authors.initials: X
authors.lastname: Qu
authors.affiliation: Department of Neurobiology, Xuzhou Medical College, Xuzhou 221004, Jiangsu, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Neurobiology, Xuzhou Medical College, Xuzhou 221004, Jiangsu, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Neurology, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, Jiangsu, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Neurobiology, Xuzhou Medical College, Xuzhou 221004, Jiangsu, China.
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Neurobiology, Xuzhou Medical College, Xuzhou 221004, Jiangsu, China.
authors.forename: Hongli
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Neurology, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, Jiangsu, China.
authors.forename: Deqin
authors.initials: D
authors.lastname: Geng
authors.affiliation: Department of Neurology, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, Jiangsu, China.
authors.forename: Hongbin
authors.initials: H
authors.lastname: Fan
authors.affiliation: Department of Neurology, Xuzhou Central Hospital, Xuzhou 221004, Jiangsu, China.
authors.forename: Qingshan
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, Jiangsu, China; Institute of Neurological Diseases of Xuzhou Medical College, Xuzhou 221002, Jiangsu, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Hua
authors.affiliation: Department of Neurobiology, Xuzhou Medical College, Xuzhou 221004, Jiangsu, China. Electronic address: wenxi_yao@163.com.
authors.forename: Ruiqin
authors.initials: R
authors.lastname: Yao
mesh_terms: D000328:Adult; D000818:Animals; D002454:Cell Differentiation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism*; D006801:Humans; D053738:Interleukin-21 Receptor alpha Subunit / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*; D009103:Multiple Sclerosis / Q000378:metabolism*; D058504:Th17 Cells
chemical_list: C508117:IL21R protein, human; C508118:Il21r protein, mouse; D053738:Interleukin-21 Receptor alpha Subunit; C546086:MIRN30b microRNA, human; D035683:MicroRNAs; C534715:Mirn30d microRNA, mouse
keywords: Demyelination; IL-21R; MiR-30a; Th17