IL-22 promotes Fas expression in oligodendrocytes and inhibits FOXP3 expression in T cells by activating the NF-κB pathway in multiple sclerosis. (February 2017)

• Record Type: Journal Article
• Authors: Zhen, Jin; Yuan, Jun; Fu, Yongwang; Zhu, Runxiu; Wang, Meiling; Chang, Hong; Zhao, Yan; Wang, Dong; Lu, Zuneng
• Is Part Of: Molecular immunology. Volume 82(2017:Feb.)
• Page Start: 84
• Page End: 93
• Publication Date: 2017-02
• Subjects: MS multiple sclerosis -- EAE experimental autoimmune encephalomyelitis -- IL interleukin -- FOXP3 transcription factor forkhead box -- HC healthy control; Multiple sclerosis -- FOXP3 -- Ikaros -- IL-22 -- Fas -- NF-κB; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2016.12.020
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: Function of IL-22 in glial cells in MS was explored in this study. Function of IL-22 in T cells in MS was explored in this study. It is the first time to indentify mechanism of IL-22 in CG4 cells and EAE development. Treg could reverse Fas expression induced by IL-22 in mouse oligodendrocytes. 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.