A novel function of RGS10 in effector T lymphocytes to augment mouse EAE (BA8P.126)

A broad range of immune-based therapeutic drugs have been available for treatment of various autoimmune diseases but many have had limited success. Therefore, it is critical to identify additional cellular targets that can regulate the pathogenic response of immune cells. We hypothesize that GPCR modulator RGS proteins are important modulators of the immune responses involved in the development of multiple sclerosis (MS). Our hypothesis is based on reports that various SNPs in RGS proteins is highly correlated with the diagnosis of MS. Especially, an in-depth search of the GEO profiles database also revealed higher levels of RGS10 transcripts in MS patients’ PBMCs. Here, we showed RGS10-null mice displayed significantly milder clinical symptoms of EAE with reduced incidence and delayed disease onset. We observed that there were less numbers of CD45+ cells and CD4+ T cells in MOG35-55-immunized RGS10-null mice in the CNS. RGS10-null LN T cells were less proliferatative and produce less IFN-γ and IL-17 cytokines in response to MOG. Our data suggest a critical role for RGS10 in modulating disease by attenuating lymphocyte infiltration and/or peripheral immune responses during EAE. This is the first study ever conducted to elucidate the function of RGS10 in effector lymphocytes in the context of EAE. The identification of RGS10 as a central regulator of the inflammatory processes will open a possibility for developing more specific targeted therapy for the treatment of MS.