Increased expression of miR-338-3p impairs Treg-mediated immunosuppression in pemphigus vulgaris by targeting RUNX1.

Abstract

Pemphigus vulgaris (PV) is a regulatory T cell (Treg)-associated autoimmune disease. Treg cells maintain immunosuppression by expressing the signature transcription factor FOXP3. MicroRNAs (miRNAs) have frequently emerged as regulators in Treg-mediated immunosuppression. We previously found that miR-338-3p was overexpressed in the peripheral blood mononuclear cells of patients with PV. Herein, we explored the role of miR-338-3p in Treg-mediated immunosuppression by quantitative real-time polymerase chain reaction, analysis of public microarray data, miRNA transfection, Western blotting, flow cytometry, and luciferase reporter assays. Increased expression of miR-338-3p was detected inCD4+T cells of active PV patients compared with those in healthy controls. Moreover, the miR-338-3p level was positively related to disease severity. Bioinformatics prediction revealed that Runt-related transcription factor 1 (RUNX1), a gene activating FOXP3 expression, was a putative target of miR-338-3p. There was a reduction of FOXP3 and RUNX1expression in the CD4+T cells of patients with PV, along with significant correlations with the level of miR-338-3p. MiRNA transfection, mRNA and protein analysis, and luciferase reporter assays verified that miR-338-3p attenuated FOXP3 expression by targeting RUNX1. This study suggests that excessive expression of miR-338-3p attenuates the expression of FOXP3by targeting RUNX1, contributing to Treg dysfunction in PV.