γδ T cell-mediated Wound Healing is Diminished by Allergic Skin Inflammation

Abstract

Atopic dermatitis results in profound changes in the function of skin that include diminished barrier function and altered production of anti-microbial peptides. Our previous work in a model of allergic skin inflammation identified a defect in the wound healing process that was dependent on IL-4. In this report we demonstrate that allergic skin inflammation results in a dramatic decrease in the presence of the Vγ3+ dendritic epidermal T cell (DETC) population of γδ T cells in the skin. In mice that express an active Stat6 in T cells, DETC are lost early in life. The loss of DETC is entirely dependent on IL-4 and is recovered with genetic-deficiency of IL-4. Moreover, injection of IL-4 into wild type mice results in acute loss of the DETC population. A similar loss of DETC was observed in mice treated topically with MC903. Wounding of skin from Stat6VT transgenic or MC903-treated mice resulted in decreased production of DETC-dependent cytokines in the skin coincident with diminished wound closure. Importantly, intradermal injection of the DETC-produced cytokine FGF7 rescued the rate of wound closure in mice with allergic skin inflammation. Together, these results suggest that the atopic environment diminishes pro-healing T cell populations in the skin that results in attenuated wound healing responses.