Epidermal T cells and wound healing

Abstract

The murine epidermis contains resident T cells that express a canonical gammadelta TCR. These cells arise from fetal thymic precursors and use a TCR that is restricted to the skin in adult animals. These cells assume a dendritic morphology in normal skin and constitutively produce low levels of cytokines that contribute to epidermal homeostasis. When skin is wounded, an unknown Ag is expressed on damaged keratinocytes. Neighboring gammadelta T cells then round up and contribute to wound healing by local production of epithelial growth factors and inflammatory cytokines. In the absence of skin gammadelta T cells, wound healing is impaired. Similarly, epidermal T cells from patients with healing wounds are activated and secreting growth factors. Patients with nonhealing wounds have a defective epidermal T cell response. Information gained on the role of epidermal-resident T cells in the mouse may provide information for development of new therapeutic approaches to wound healing.

Figure 1

DETC arise from fetal thymic precursors. TCR γ and δ chains are expressed in an ordered manner during development, with waves of cells expressing distinct γδ TCR exiting the thymus to populate specific epithelial tissues. The Vγ3Vδ1 TCR is rearranged and expressed early in fetal ontogeny. These cells migrate to the skin where they assume a dendritic morphology and persist in the adult mouse.

Figure 2

DETC morphology changes in response to tissue damage. DETC present in normal epidermis (A) have a dendritic morphology. DETC located around a wound (B) become rounded and this morphology change correlates with initiation of a functional response. Epidermal sheets from a C57BL/6J mouse were stained with PE-anti-γδ TCR (mAb GL-3) and confocal images were acquired with a 40X objective.

Figure 3

Model of DETC functions during skin homeostasis and wound healing. DETC secrete low levels of cytokines in normal skin that contribute to epithelial homeostasis. Unknown antigens for DETC are expressed on keratinocytes in wounded tissue. DETC recognition of antigen and costimulation through molecules like JAML binding CAR leads to DETC rounding and activation to produce cytokines, growth factors and chemokines that contribute to a wound healing response.