Natural killer cells as key regulators of cutaneous wound healing

Abstract

Abstract Annually in the U.S, the cost to treat the more than 6 million sufferers of chronic, non-healing wounds exceeds 50 billion U.S.D. Despite extensive characterization of the functionally diverse cellular and molecular constituents found in the wound bed, wound healing therapies are lacking. The pro- and anti-inflammatory capabilities of the innate immune system make it critical in the wound healing process. Natural killer (NK) cells are innate lymphocytes which exhibit similar pro- and anti-inflammatory capabilities. Despite the breadth of their functions, ranging from anti-microbial to maintaining a healthy pregnancy, there is a paucity of information regarding NK cells in the wound healing process. Using mouse wound models, we have identified 2 distinct populations of NK cells abundantly present in seven-day old sterile, cutaneous wounds. In addition, we have identified NK cells in the wound effluent of patients who underwent corrective surgery for idiopathic scoliosis. Previous work in different models suggests that these 2 NK cell populations exhibit proliferative effector functions related to their potential to facilitate organogenesis and T cell activation. Interestingly, these are both processes implicated in late stage wound healing. Using our mouse model of cutaneous wound healing we have shown that NK cell depletion delays closure. Furthermore, we show that NK cell depleted wounds demonstrate an aberrant growth factor response. With this work we aim to determine the impacts wound natural killer cell phenotype and function have on cutaneous wound healing outcomes and to determine the role of natural killer cells in wound growth factor expression.