March1-overexpressed dendritic cells downregulate Th1/Th2 ratio in asthma through promoting OX40L

Abstract

Asthma is an inflammatory disease. Th2 differentiation plays an important role in the pathogenesis of asthma. We explored the role and action mechanism of membrane-associated RING-CH 1 (March1) in the Th2 differentiation regulated by dendritic cells (DCs). Our data showed that the expression of March1 was higher in asthmatic children-derived DCs, asthmatic mice-derived DCs and house dust mites (HDMs)-treated DCs than that in control DCs. Increasing of March1 promoted the production of pro-inflammatory cytokines from HDMs-treated DCs, and enhanced the promotion of HDMs-treated DCs to CD4+T cell proliferation and Th2 differentiation, whereas decreasing of March1 resulted in opposite effects. Furthermore, our data indicated that March1 positively regulated the expression of OX40 ligand (OX40L) and facilitated DCs-induced Th2 differentiation through OX40L. In asthmatic mice, March1-overexpressed DCs significantly aggravated the injury in lung tissues and promoted Th2 differentiation. Overall, our data proved that highly expressed March1 in DCs facilitated asthma development through inducing Th2 differentiation by facilitating OX40L expression. Our data might provide a new idea for the treatment of asthma.