Gamma delta T cells comprise a major T cell component in epithelial tissues. The tight correlation between TCR V gene segment usage and tissue localization suggest a specialized function for these cells that is distinct from that of conventional alpha beta and gamma delta T cells of the hematolymphoid tissues. We have demonstrated that gamma delta T cell receptor-bearing dendritic epidermal T cells (DETC) found in murine skin recognize antigen expressed by damaged or stressed skin keratinocytes raising the possibility that DETC play a role in tissue repair. Little is known about functions of epithelial resident gamma delta T cells and their role in wound repair has not been examined. We have initiated wound healing studies and found defects in keratinocyte proliferation, tissue reepithelialization, and cell migration into wounded tissue in the absence of DETC. We propose to identify the functional role of the DETC in these processes and determine the mechanisms of their participation. The contribution of DETC to various stages of wound repair through the production of KGF-1, KGF-2, and chemokines in injured skin will be defined. The role of DETC antigen expression by damaged keratinocytes in initiation of the DETC wound healing response will be assessed. We propose that DETC play a unique role in epithelial tissue repair. No clear specialized functions have been described for yd T cells, which should make these studies of interest.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI036964-06
Application #
6510563
Study Section
Immunological Sciences Study Section (IMS)
Program Officer
Hackett, Charles J
Project Start
1996-04-01
Project End
2006-03-31
Budget Start
2002-04-01
Budget End
2003-03-31
Support Year
6
Fiscal Year
2002
Total Cost
$310,275
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Lee, Pedro; Gund, Rupali; Dutta, Abhik et al. (2017) Stimulation of hair follicle stem cell proliferation through an IL-1 dependent activation of ??T-cells. Elife 6:
Nielsen, Morten M; Witherden, Deborah A; Havran, Wendy L (2017) ?? T cells in homeostasis and host defence of epithelial barrier tissues. Nat Rev Immunol 17:733-745
Ramirez, Kevin; Witherden, Deborah A; Havran, Wendy L (2015) All hands on DE(T)C: Epithelial-resident ?? T cells respond to tissue injury. Cell Immunol 296:57-61
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 135:1311-1319
Nielsen, Morten M; Lovato, Paola; MacLeod, Amanda S et al. (2014) IL-1?-dependent activation of dendritic epidermal T cells in contact hypersensitivity. J Immunol 192:2975-83
Meehan, T F; Witherden, D A; Kim, C-H et al. (2014) Protection against colitis by CD100-dependent modulation of intraepithelial ?? T lymphocyte function. Mucosal Immunol 7:134-42
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
Witherden, Deborah A; Havran, Wendy L (2013) Cross-talk between intraepithelial ?? 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 ýýýý T cell ligands are rapidly and locally expressed by keratinocytes following cutaneous wounding. J Immunol 188:2972-6

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