There is a resident population of T cells found in murine skin that expresses an invariant V?3V?1 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. A population of ?? 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. A population of ?? 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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI036964-14
Application #
8260588
Study Section
Cellular and Molecular Immunology - B Study Section (CMIB)
Program Officer
Miller, Lara R
Project Start
1996-05-15
Project End
2014-04-30
Budget Start
2012-05-01
Budget End
2014-04-30
Support Year
14
Fiscal Year
2012
Total Cost
$417,891
Indirect Cost
$197,368
Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037
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