IL-6/STAT3 pathway induced deficiency of RFX1 contributes to Th17-dependent autoimmune diseases via epigenetic regulation.

ABSTRACT: Epigenetic modifications affect the differentiation of T cell subsets and the pathogenesis of autoimmune diseases, but many mechanisms of epigenetic regulation of T cell differentiation are unclear. Here we show reduced expression of the transcription factor RFX1 in CD4⁺ T cells from patients with systemic lupus erythematosus, which leads to IL-17A overexpression through increased histone H3 acetylation and decreased DNA methylation and H3K9 tri-methylation. Conditional deletion of Rfx1 in mice exacerbates experimental autoimmune encephalomyelitis and pristane-induced lupus-like syndrome and increases induction of Th17 cells. In vitro, Rfx1 deficiency increases the differentiation of naive CD4⁺ T cells into Th17 cells, but this effect can be reversed by forced express

SUBMITTER: Zhao M 

PROVIDER: S-EPMC5805701 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature