There is a resident population of T cells found in murine skin that expresses an invariant V33V41 TCR. These dendritic epidermal T cells (DETC) are in constant contact with neighboring epithelial cells. The keratinocytes have a rapid rate of turnover as they constantly differentiate and renew the epithelium. DETC remain at a steady-state density in the skin of mice until epithelial damage or disease occurs. DETC then lose their dendritic shape and round-up, become activated, increase in numbers, and secrete cytokines and chemokines that impact tissue repair. Following resolution of the damage, DETC return to steady-state numbers, downregulate expression of many cytokines, and regain their dendritic shape. Little is known about the mechanisms that regulate DETC homeostasis. During the next grant period we propose to determine the requirements for homeostasis of the DETC under steady-state conditions and to identify mechanisms that positively or negatively regulate the restoration of the DETC homeostatic state following resolution of skin trauma.
Three specific aims will investigate the role of cytokines in the regulation of DETC homeostatic proliferation, cell contact- mediated mechanisms of DETC homeostasis, and the requirements for restoration of DETC homeostasis following skin damage or disease. Public Health Relevance: A population of 34 T cells resides in the skin and have specialized functions in tissue homeostasis, killing of malignant cells, and wound healing. It is important to understand the processes that regulate the lifespan and functional status of these cells in order to develop strategies for using these cells to fight skin tumors and improve the healing process for chronic wounds.
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