Hypomethylation ofIL10andIL13Promoters in CD4+T Cells of Patients with Systemic Lupus Erythematosus

Abstract

Interleukin- (IL-)10 and IL-13 play important roles in Th2 cell differentiation and production of autoantibodies in patients with (SLE). However, the mechanisms leading toIL10andIL13overexpression in SLE patients are not well understood. In this study, we confirm that the levels of bothIL10andIL13mRNA in CD4+T cells and of serumIL10andIL13proteins are increased in SLE patients. We show that the DNA methylation levels withinIL10andIL13gene regulatory domains are reduced in SLE CD4+T cells relative to healthy controls and negatively correlate withIL10andIL13mRNA expression. Moreover, treating healthy CD4+T cells with the demethylating agent 5-azacytidine (5-azaC) increasedIL10andIL13mRNA transcription. Together, our results show that promoter methylation is a determinant ofIL10andIL13expression in CD4+T cells, and we propose that DNA hypomethylation leads toIL10andIL13overexpression in SLE patients.