Central theme in T cell development is to eliminate self-reactive T cells, whereas to maintain the T cells reactive to foreign antigens. During T cell development, more than 95% of the T cells are eventually eliminated by a programmed cell death (apoptosis). We have demonstrated that RORg plays a critical role in this apoptotic process. However, the mechanisms responsible for RORg-regulated apoptosis are largely unknown. RORg recruits a family of proteins called SRCs to regulate thymocyte survival. We are in the process of identifying RORg target genes, as well as RORg upstream regulators. Our study will facilitate the understanding a novel role of RORg in instructing the differentiation of Th17 cells, essential effectors in autoimmunity .
Cellular function in multiple cell organisms depends on coordinated cell to cell communication. b-catenin pathway is one of such critical molecules used to communicate between cells. We have demonstrated that b-catenin pathway mediates the critical survival signals for thymocytes as well as responsible for up-regulating a critical molecule, CD4, on thymocytes. We are in the process of studying how b-catenin pathway regulates thymocyte survival as well as T cell activation.
The first step in initiating immune responses against pathogens is T cell activation. PKC-q is required for T cell activation process. In addition, PKC-q mediates the survival signals during T cell activation process. Recently, we have identified the function of PKC-q in eliminating T cells via activation-induced cell death. We are currently studying the function of PKC-q in T cell-mediated rejection of allografts. Our results demonstrated that PKC-q is required to mediate the immune responses for allograft rejection. Therefore, PKC-q is a potential drug target for preventing allograft rejection. Currently, we are elucidating the molecular mechanisms responsible for PKC-q-regulated T cell functions.