Contribution of Invariant Natural Killer T Cells to Skin Wound Healing

In the present study, we determined the contribution of invariant natural killer T (iNKT) cells to the skin wound healing process. In iNKT cell-deficient (J alpha 18K0) mice lacking iNKT cells, wound closure was significantly delayed compared with wild-type mice. Collagen deposition, expression of alpha-smooth muscle actin and CD31, and wound breaking strength were significantly attenuated in J alpha 18K0 mice. The adoptive transfer of Liver mononuclear cells from wild-type but not from J alpha 18K0 or interferon (IFN)-gamma gene-disrupted (IFN-gamma K0) mice resulted in the reversal of this impaired wound healing in J alpha 18K0 mice. IFN-gamma expression was induced in the wounded tissues, which was significantly decreased at 6, 12, and 24 hours, but increased on day 3 after wounding in J alpha 18K0 mice. The main source of the Late-phase IFN-gamma production in J alpha 18K0 mice were neutrophils rather than NK cells and T cells. Administration of alpha-galactosylceramide, an activator of iNKT cells, resulted in the acceleration of wound healing on day 3 in wild-type mice. This effect was not observed in IFN-gamma K0 mice. These results indicate that iNKT cells play important roles in wound healing. The iNKT cell-induced IFN-gamma production may regulate the wound healing process in the early phase.