Exploratory Study of T Cell Skin Trafficking and the Role of NKG2D Signaling; Implications in Vitiligo and Melanoma

点击翻译按钮获取中文摘要

Abstract In the field of immunology, T cell migration is considered crucial for long-term host survival. However, the identity of the players that participate and the mechanistic relationships in this complex network remain to be fully established, especially in the context of vitiligo and melanoma. Our understanding of the T cell migratory properties and initiation ques may help find clinically applicable treatments to vitiligo and melanoma. Based on novel preliminary data, we propose to study NKG2D signaling as a contributor to T cell trafficking. The scientific premise of this study is derived from our work demonstrating that lack of NKG2D reduces T cell tmigration and expression of CCR4. We hypothesize that NKG2D controls CD8 T cell trafficking through a finely tuned DAP10PI3K/Grb2 signaling (as NKG2D cannot signal by itself instead of using DAP10PI3K/Grb2 as signaling adaptor) that controls the expression of CCR4. This proposal will define the underlying roles of NKG2D-DAP10PI3K and -DAP10Grb2 in CD8 T cell trafficking and the expression control of CCR4. Here we will conduct experimental tests utilizing human and mouse models. SA1. TO DETERMINE THE SIGNALING PATH FOR NKG2D-DAP10PI3K and/or -DAP10Grb2 THAT CONTROLS CCR4 EXPRESSION. SA2. TO DETERMINE THE SPECIFIC CONTRIBUTION OF NKG2D-DAP10PI3K and/or -DAP10Grb2 SIGNALING IN THE SKIN TRAFFIC OF CD8 T CELLS.