Epithelial and bone marrow derived sources of Cd1d contribute to wound repair

Abstract

Abstract Wound healing is a multifaceted process that depends on both epithelial and bone marrow derived cells to promote proper healing. Recent publications have shown that a subset of T cells in the skin are activated by certain lipids bound to CD1 molecules. Cd1d, the isoform of CD1 expressed in mice, is an MHC-like molecule that binds lipid antigens and is expressed by Langerhans cells (LCs), macrophages, B cells, and wounded keratinocytes. As our lab has previously shown that T cell activation in the skin promotes wound healing, we hypothesize that Cd1d is an important component of normal wound healing. To investigate this hypothesis, we administered full thickness wounds to the dorsal skin of WT and Cd1d−/− mice and analyzed wound closure. Cd1d−/− mice had a significant delay in wound healing between days 1 and 5 compared to WT controls. Analysis of ex vivo wound healing failed to show any difference in wound closure rates between WT and Cd1d−/− skin. This suggested that an infiltrating cell type is at least partially responsible for the observed difference in in vivo wound healing. Transfer of WT bone marrow cells into lethally irradiated Cd1d−/− mice did not rescue the wound healing defect observed in Cd1d−/− mice. Interestingly, transfer of Cd1d−/− bone marrow into WT mice caused a delay in wound healing. Analysis of wounded skin demonstrated that significantly fewer macrophages and LCs were present in Cd1d−/− epidermis. We conclude that the Cd1d-mediated wound healing defect is dependent on both resident LCs and infiltrating macrophages, and continue to investigate how Cd1d expressed by LCs promotes wound repair as studies have shown that LCs have an immunosuppressive effect in models of contact hypersensitivity and UVB-induced inflammation.