Background MicroRNA (miR) as a class of regulatory elements are plays important role in various autoimmune diseases, including rheumatoid arthritis.MiR-155 has been demonstrated as a central regulator of the autoimmune system, but its function during autoimmune arthritis is still poorly understood.
Objectives To clarify the function of miR-155 in CD4+regulatory Th17 cell differentiation, as well as the mechanism involved in autoimmune arthritiTo clarify the function of miR-155 in CD4+regulatory Th17 cell differentiation, as well as the mechanism involved in autoimmune arthritis.
Methods In vitro, CD4+ cell was isolated from DAB1 mice' spleen. We performed gain-and-loss-of-function analysis by transfection miR-155 mimics and miR-155 inhibitors into purified CD4+T cells. Also, we used RNA interference to silence Ets-1 gene expression. In addition, in vivo, up regulation of miR-155 expression by lent virus miR-155 (LV-miR-155) infection and silencing of miR-155 expression by lent virus-anti-miR-155 (LV-anti-miR-155) was researched in the experimental mice with type II collagen (CII)-induced arthritis (CIA). The ratio of IL-17 was analyzed using flow cyctometry (FCM).The related gene expression such as Foxp3, RORgt, IFN-g, Ets-1and stat3 was detected by Quantitative Real-time PCR (qPCR) and western blotting.
Results The result showed that miR-155 promoted Th17 cell differentiation. It also induced related gene expression, such as Foxp3, RORgt, IFN-g and stat3; it inhibited Ets-1 gene expression. This may because miR-155 modulates Th-17 cell differentiation by targeting Ets-1.Here we identify miR-155 was highly correlated with disease in mice with experimental CIA. In vivo over expression of miR-155 led to more Th-17cells and severe CIA, and the related genes were higher express, but Ets-1 was lower expression. In contrast, the down regulation of miR-155 expression resulted in fewer Th17 cells and Normal mice. The related genes were lower express, but Ets-1 was higher expression.
Conclusions Our data show a critical role for miR-155 in Th17 differentiation and the pathogenesis of autoimmune arthritis, and it might be involved in the occurrence and development of autoimmune diseases in rheumatoid arthritis.
Disclosure of Interest None declared