The Rai adaptor protein in Th17 cell differentiation, effector function and chemotaxis and in the pathogenesis of multiple sclerosis

Background We have previously reported that Rai deficiency in the mouse results in the development of lupus-like autoimmunity and showed that this could be accounted for, at least in part, by the function of Rai as an attenuator of antigen receptor signaling, such that Rai deficient T and B lymphocytes displayed spontaneous activation and proliferation and enhanced responses to antigen both in vitro and in vivo compared to wild-type controls (Savino et al. 2009). Based on the central implication of Th1 and Th17 cells in the pathogenesis of a wide range of autoimmune disorders, including lupus, multiple sclerosis and rheumatoid arthritis, we asked whether Rai could regulate not only the activation of T cells, but also their development to these proinflammatory effectors. Aim of the project The principal objectives of this project are: i) to assess the role of Rai on the differentiation, activation and chemotaxis of CD4+ T cell subsets; ii) to translate the results to the pathogenesis of multiple sclerosis.