Simvastatin and ROCK inhibition in Th0 and Th17 systems

Purpose The deregulation of the Def6-ROCK2-IRF4 axis in murine models results in both lupus-like and rheumatoid arthritis-like disease characterized by increased IL-17 and IL-21 production that is ameliorated by ROCK inhibition. A known beneficial pleiotropic effect of statins is inhibition of ROCK activation via their effect on RhoA activation. Statins have also been reported to decrease IL-17 and IL-21 production in T cells. Whether statins exert their inhibitory effects by interfering with the ROCK2-IRF-4 interaction in CD4+ T cells is unknown. The aim of the present study is to investigate whether statins can inhibit the ROCK pathway in CD4+ T cells and inhibit IL-17 and IL-21 production.