Systemic sclerosis (SSc) is a chronic connective tissue disease characterized by autoimmunity, vasculopathy and fibrosis. Both in vivo and in vitro evidence suggest that the anti-AT1R autoantibodies play a role in the pathogenesis of SSc. These autoantibodies offer a novel perspective to investigate mechanisms of SSc.

We have established a novel mouse model of SSc by immunizing mice with human AT1R. This mouse model convinces that autoimmunity to AT1R plays an essential role in SSc pathogenesis. This project will generate and characterize monoclonal antibodies against AT1R, verifying the hypothesis that the stimulating antibodies against the AT1R play a pathogenic role in SSc. In addition, identification of the pathogenic monoclonal antibodies against AT1R will provide a novel mouse model of SSc by transfer those antibodies into mice. Furthermore, we will investigate the mechanism of role the AT1R signaling in the pathogenesis of SSc using the abovementioned passive transfer mosue model of SSc.