MicroRNA-125b regulates Th17/Treg cell differentiation and is associated with juvenile idiopathic arthritis

Background Juvenile idiopathic arthritis(JIA)is the most common rheumatic disease in childhood driven by aberrant pathways of T-cell activation.T helper 17(Th17)/regulatory T cell(Treg)imbalance plays critical roles in the pathogenesis of arthritis.MicroRNA-125b(miR-125b)was upregulated after the activation of the initial CD4^+T cells,and could regulate the differentiation of CD4^+T cells.However,the effects of miR-125b on Th17/Treg imbalance and differentiation of Th 17/Treg cells remain unknown.Methods In this study,we evaluated the expression of miR-125b in the peripheral blood mononuclear cells(PBMCs)of children with JIA,and the relationship of miR-125b with Th17/Treg imbalance.Then,we used lentivirus vector-mediated overexpression technology to investigate the regulatory function of miR-125b in CD4^+T cells or dendritic cell/CD4^+T co-culture system.Results Decreased miR-125b expression in PBMCs and CD4^+T cells of JIA patients was negatively correlated with the ratio of Th17/Treg cells.It also correlated negatively with retinoic acid receptor-related orphan receptorγt but positively with Forkhead box protein 3 at transcriptional levels.Furthermore,we found that miR-125b overexpression inhibited Th17 cell differentiation,whereas facilitated the differentiation of Treg cells.MiR-125b upregulation led to the decrease of Th 17-secreting cytokines but the increase of the Treg-secreting cytokines.Conclusions Our results demonstrate that miR-125b participated in regulating Thl7/Treg cell differentiation and imbalance in JIA patients.These findings provide novel insight into the critical role of miR-125b in the Th17/Treg imbalance of JIA,and raise the distinct possibility that miR-125b may prove to be a potential therapeutic target for JIA.