Neutrophils and natural killer T cells as negative regulators of wound healing

Abstract

Cutaneous wound healing is a dynamic process requiring coordination of immune cell infiltration, keratinocyte proliferation, angiogenesis, extracellular matrix deposition and remodeling to ensure adequate wound closure [1–3]. Multiple pathologic conditions are known to perturb efficient cutaneous repair by impacting one or more of the three interdependent phases of wound healing: the early inflammatory, proliferative, or late remodeling phase [1,2,4,5]. Innate immune cells are critical during wound repair, as innate immune cell dysfunction has been demonstrated to augment normal wound healing, leading to poor wound closure or hypertrophic scar formation. While several immune cells, in particular macrophages, dendritic epidermal T cells (DETCs) and mast cells, have all been demonstrated to enhance aseptic wound healing [6–15], two members of the innate immune population, neutrophils and natural killer T (NKT) cells, act to negatively regulate the pace of wound closure. Herein, we focus our discussion on the negative regulatory role of these neutrophils and NKT cells, and consider potential therapeutic interventions that may enhance wound repair by alterations in the number or function of these populations.