Atg7 plays a critical role in the development of iNKT cells with altered PLZF expression. (HEM8P.242)

Abstract

Abstract Invariant Natural Killer T (iNKT) cell is a distinct subset of T cells that plays a regulatory role in various immune diseases. Although many studies have reported that various factors regulate development of iNKT cells, the role of autophagy in the development is still unknown. Here, we report that autophagy-related protein 7(Atg7) is required for development of iNKT cells in the thymus. iNKT cells of the thymus and liver expressed Atg7 and their development is completely attenuated in the thymus of CD4-specific Atg7 knock-out (CD4-Cre/Atg7f/f) mice compared with WT mice. The levels of PLZF expression were altered in thymocytes from CD4-Cre/Atg7f/f mice as compared with WT mice. CD4-Cre/Atg7f/f mice showed a few iNKT cells in peripheral organs, which led to functional deficient in iNKT cell-specific activation in vitro and in vivo. Accordingly, autoantibody-induced arthritis was attenuated in CD4-Cre/Atg7f/f mice. Therefore, our findings suggest that Atg7 regulates iNKT cell development with altered PLZF expression.