부산대학교 도서관

Rai prevents lupus nephritis by impairing the development and expansion of both proinflammatory Th17 and Th1 cells. Rai, a Shc adapter family member, acts as a negative regulator of antigen receptor signaling in T and B cells. Rai−/−mice develop lupus‐like autoimmunity associated to the spontaneous activation of self‐reactive lymphocytes. Here, we have addressed the potential role of Rai in the development of the proinflammatory Th1 and Th17 subsets, which are centrally implicated in the pathogenesis of a number of autoimmune diseases, including lupus. We show that Rai−/−mice display a spontaneous Th1/Th17 bias. In vitro polarization experiments on naive and effector/memory CD4+T cells demonstrate that Rai−/−favors the development and expansion of Th17 but not Th1 cells, indicating that Rai modulates TCR signaling to antagonize the pathways driving naive CD4+T cell differentiation to the Th17 lineage, while indirectly limiting Th1 cell development in vivo. Th1 and Th17 cell infiltrates were found in the kidneys of Rai−/−mice, providing evidence that Rai−/−contributes to the development of lupus nephritis, not only by enhancing lymphocyte activation but also by promoting the development and expansion of proinflammatory effector T cells. Interestingly, T cells from SLE patients were found to have a defect in Rai expression, suggesting a role for Rai in disease pathogenesis.