Carnosol Alleviates Collagen-Induced Arthritis by Inhibiting Th17-Mediated Immunity and Favoring Suppressive Activity of Regulatory T Cells

Abstract

Current approaches are incurable for rheumatoid arthritis (RA). Regulatory T (Treg) cells and T helper cells (Th1 and Th17) are crucial in controlling the process of RA, which is characterized by inflammatory cell infiltration and bone destruction. Carnosol is an orthodiphenolic diterpene that has been extensively applied in traditional medicine for the treatment of multiple autoimmune and inflammatory diseases. Herein, we indicate that administration of carnosol dramatically alleviated the severity of collagen-induced arthritis (CIA) model with a decreased clinical score and inflammation reduction. Cellular mechanistically, carnosol inhibits the Th17 cell differentiation and maintains Treg cell suppressive function in vitro and in vivo. Meanwhile, it also restrains Treg cells from transdifferentiation into Th17 cells under inflammatory milieu. Furthermore, carnosol modulates the function of Th17 and Treg cells possibly via limiting IL-6R (CD126) expression. Collectively, our results suggest that carnosol can alleviate the severity of CIA via hiding Th17 cell differentiation and maintain the stability of Treg cells. Administration of carnosol can be applied as a potential therapy for patients with RA.