title: IL-22 promotes Fas expression in oligodendrocytes and inhibits FOXP3 expression in T cells by activating the NF-κB pathway in multiple sclerosis.
abstract: Multiple sclerosis (MS) is characterized by an increase in interleukin-22 and Fas, and a decrease in FOXP3, among other factors. In this study, we examined patients with MS and healthy control subjects and used the experimental autoimmune encephalomyelitis (EAE) animal model to identify the effects of IL-22 on oligodendrocytes and T cells in MS development. In MS, the expression of Fas in oligodendrocytes and IL-22 in CD4+CCR4+CCR6+CCR10+T cells was enhanced. Ikaros and FOXP3 were both decreased in T cells. Depending on exogenous IL-22, Fas increased the phosphorylation of mitogen- and stress-activated protein kinase 1 and activated the nuclear factor-κB pathway in oligodendrocytes, leading to an increase in Fas and oligodendrocyte apoptosis. IL-22 decreased FOXP3 expression by activating NF-κB, and it further inhibited PTEN and Ikaros expression. Tregs reversed the functions of IL-22. Taken together, these findings help to elucidate the mechanisms of IL-22 in MS development.
authors.affiliation: Department of Neurology, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, Hubei 430060, PR China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhen
authors.affiliation: Department of Neurology, Inner Mongolia Autonomous Region People's Hospital, Hohhot, 010000, Inner Mongolia, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Department of Neurology, Inner Mongolia Autonomous Region People's Hospital, Hohhot, 010000, Inner Mongolia, PR China.
authors.forename: Yongwang
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Department of Neurology, Inner Mongolia Autonomous Region People's Hospital, Hohhot, 010000, Inner Mongolia, PR China.
authors.forename: Runxiu
authors.initials: R
authors.lastname: Zhu
authors.affiliation: Department of Neurology, Inner Mongolia Autonomous Region People's Hospital, Hohhot, 010000, Inner Mongolia, PR China.
authors.forename: Meiling
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Neurology, Inner Mongolia Autonomous Region People's Hospital, Hohhot, 010000, Inner Mongolia, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Chang
authors.affiliation: Department of Neurology, Inner Mongolia Autonomous Region People's Hospital, Hohhot, 010000, Inner Mongolia, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Neurology, Inner Mongolia Autonomous Region People's Hospital, Hohhot, 010000, Inner Mongolia, PR China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Neurology, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, Hubei 430060, PR China. Electronic address: zhenjin2015@yeah.net.
authors.forename: Zuneng
authors.initials: Z
authors.lastname: Lu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007378:Interleukins / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D009103:Multiple Sclerosis / Q000276:immunology* / Q000378:metabolism; D016328:NF-kappa B / Q000276:immunology; D009836:Oligodendroglia / Q000276:immunology / Q000378:metabolism; D016133:Polymerase Chain Reaction; D051381:Rats; D015398:Signal Transduction / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D019014:fas Receptor / Q000096:biosynthesis* / Q000276:immunology; D000097043:Interleukin-22
chemical_list: D051858:Forkhead Transcription Factors; D007378:Interleukins; D016328:NF-kappa B; D019014:fas Receptor; D000097043:Interleukin-22
keywords: FOXP3; Fas; IL-22; Ikaros; Multiple sclerosis; NF-κB