Visualization of gamma delta T cells in wound healing

Scripps Research Institute, La Jolla CA

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Abstract

DESCRIPTION (provided by applicant): Thy-1+ dendritic epidermal T cells (DETC) found in murine skin express a monoclonal gammadelta T cell receptor and recognize an unknown antigen expressed by damaged keratinocytes. We have shown that DETC play an important role in wound healing by producing factors that impact keratinocyte proliferation, tissue reepithelialization, and wound closure. DETC located around the wound exhibit a change in morphology characterized by a loss of the distinctive dendritic morphology that correlates with their activation and participation in wound repair. We hypothesize that interactions between Plexin-B2 on keratinocytes and the semaphorin CD100 (SEMA4D) on neighboring DETC deliver signals that lead to cytoskeletal rearrangements and movement of DETC and keratinocytes to wound sites. Clues to the mechanisms involved may come from the function and mode of action of plexins and semaphorins in the nervous system where these molecules are involved in processes that include axonal repulsion and attraction, cytoskeletal rearrangements and modulation of cell morphology and motility. Visualization of interactions mediated by these molecules may reveal new similarities between the immune and nervous systems, where semaphorin/plexin interactions are well characterized, that will provide insights into mechanisms of tissue remodeling and repair. Experiments proposed are exploratory in nature and involve the use of live cell imaging in real time. Interesting initial results from this study will lead to new directions aimed at dissection of immune responses in epithelial tissues.