Effects of Rho GTPase CDC42 on Th2 and Th17 differentiation (CCR6P.277)

Abstract

Abstract We have reported that cell-division-cycle 42 (CDC42) of Rho GTPase family was important for T cell development and homeostasis with the use of conditional CDC42-deficient mice (CDC42flox/LckCre), in which CDC42 was deleted in CD4-CD8- double negative stage of thymocytes. Recently, we generated another line of conditional CDC42-deficient mice with selective expression of the Cre recombinase beginning at a late stage of T cell development (after positive selection of CD4+CD8+) using the distal promoter of the Lck (dLck) gene. We found that CDC42-deficiency (CDC42flox/dLckCre) did not affect T cell development, as expected. The development of natural regulatory T cells (nTreg) was also not affected by CDC42-deficiency. However, CDC42-deficiency impaired in vitro activation of both CD4+ and CD8+ T cells. When naïve CD4+ T cells were cultured under non-polarized conditions, CDC42-deficiency significantly reduced Th1 and Th2 cytokine secretion, but slightly increased Th17 cytokine secretion from CD4+ T cells. Under Th1/Th2/Th17-polarized conditions, CDC42-deficiency significantly downregulated Th2-differentiation, but was less effective to Th1 and Th17 differentiation. CDC42 has no significant role on the induction of Treg in vitro. The ongoing studies are trying to explore the underlying molecular mechanisms. Our findings suggest that CDC42 of Rho GTPase is not only crucial for T cell development and activation, but also involved in Th differentiation, especially Th2 cells.