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.
|Nielsen, Morten M; Dyring-Andersen, Beatrice; Schmidt, Jonas D et al. (2015) NKG2D-dependent activation of dendritic epidermal T cells in contact hypersensitivity. J Invest Dermatol 135:1311-9|
|Ramirez, Kevin; Witherden, Deborah A; Havran, Wendy L (2015) All hands on DE(T)C: Epithelial-resident Î³Î´ T cells respond to tissue injury. Cell Immunol 296:57-61|
|MacLeod, Amanda S; Rudolph, Ross; Corriden, Ross et al. (2014) Skin-resident T cells sense ultraviolet radiation-induced injury and contribute to DNA repair. J Immunol 192:5695-702|
|Meehan, T F; Witherden, D A; Kim, C-H et al. (2014) Protection against colitis by CD100-dependent modulation of intraepithelial Î³Î´ T lymphocyte function. Mucosal Immunol 7:134-42|
|Nielsen, Morten M; Lovato, Paola; MacLeod, Amanda S et al. (2014) IL-1Î²-dependent activation of dendritic epidermal T cells in contact hypersensitivity. J Immunol 192:2975-83|
|Witherden, Deborah A; Havran, Wendy L (2013) Cross-talk between intraepithelial Î³Î´ T cells and epithelial cells. J Leukoc Biol 94:69-76|
|MacLeod, Amanda S; Hemmers, Saskia; Garijo, Olivia et al. (2013) Dendritic epidermal T cells regulate skin antimicrobial barrier function. J Clin Invest 123:4364-74|
|Komori, H Kiyomi; Witherden, Deborah A; Kelly, Ryan et al. (2012) Cutting edge: dendritic epidermal Ã½Ã½Ã½Ã½ T cell ligands are rapidly and locally expressed by keratinocytes following cutaneous wounding. J Immunol 188:2972-6|
|Witherden, Deborah A; Watanabe, Megumi; Garijo, Olivia et al. (2012) The CD100 receptor interacts with its plexin B2 ligand to regulate epidermal Ã½Ã½Ã½Ã½ T cell function. Immunity 37:314-25|
|Macleod, Amanda S; Havran, Wendy L (2011) Functions of skin-resident Î³Î´ T cells. Cell Mol Life Sci 68:2399-408|
Showing the most recent 10 out of 26 publications