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-22and 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 oligodendrocytesand T cells in MS development. In MS, the expression of Fas in oligodendrocytesand IL-22 in CD4 + CCR4+ CCR6 + CCR10+ T cells was enhanced. Ikaros and FOXP3were 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 oligodendrocyteapoptosis. IL-22 decreased FOXP3expression 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.