MiR-29b interacts with IFN-γ and induces DNA hypomethylation in CD4+ T cells of oral lichen planus

Abstract

Oral lichen planus (OLP) is an autoimmune inflammatory disease mediated by T cells, in whose pathogenesis CD4⁺ T helper cells are supposed to play vital roles. MiR-29b has recently been recognized as a crucial regulator in immune response and inflammation. The current research focuses on exploring how miR-29b functions in the immunopathogenesis of OLP. Our findings showed that miR-29b expression in CD4⁺ T cells was upregulated in OLP, especially in its erosive form. MiR-29b in CD4⁺ T cells repressed IFN-γ mRNA and IFN-γ secretion, but not T-bet and EOMES; in turn, IFN-γ increased the expression of STAT1 and miR-29b in CD4⁺ T cells. Moreover, miR-29b in CD4⁺ T cells suppressed DNMT1 expression and induced global DNA hypomethylation. In conclusion, elevated miR-29b interacts with IFN-γ via a regulatory feedback loop and induces global DNA hypomethylation in CD4⁺ T cells, which consequently modulates Type 1 T helper immune response, thus contributing to the immune dysregulation of OLP.

Keywords: CD4(+) T cells; DNA methylation; IFN-γ; Oral lichen planus; miR-29b.