Research Technician Brown Univ. Providence, Rhode Island, United States
Disclosure(s):
Fiona Jameson: No financial relationships to disclose
Introduction/Rationale: Chronic poor wound healing is a significant global health burden, contributing to morbidity and mortality. Natural killer (NK) cells are innate lymphoid cells that possess both cytotoxic and infection-clearing roles. In the context of tissue repair, NK cells have been shown to have interactions with endothelial cells in the modulation of fibrosis and in the process of re-epithelialization. Consequently, NK cells may have the potential to influence the process of wound healing. The few studies that have examined NK cells’ role in wound healing have generated conflicting results, with one study reporting that NK cell ablation accelerates wound closure while another stated that NK cells have a positive role by limiting the acute inflammatory reaction to wounding. We investigate the role of NK cells as regulators of wound healing using multiple mouse models of skin injury.
Methods: Our data established the kinetics of NK cell recruitment in the wound with flow cytometry and characterized a unique phenotype that wound NK cells possess. Two mouse models of wound closure, a dorsal punch biopsy and tail-excisional wound, were used in conjunction with a NK-depleting antibody to measure the rate of wound closure in the absence of NK cells.
Results: The tail-excisional model, which heals primarily by re- epithelialization, demonstrated that wound closure is slower in the absence of NK cells. However, in the punch biopsy model, which relies on the contraction of skin to heal, NK depletion had no significant impact on the rate of wound closure. Using a model that allowed for the analysis of wound cells and fluid, we found that the growth factors EGF and VEGF were increased in the absence of NK cells. RNAseq data of NK-depleted mice showed the overexpression of collagen production genes related to skin and vasculature development.
Conclusion: This work contributes to the wound healing field by furthering insights regarding NK cells’ influence on wound closure, re-epithelialization, and vascularization.
