Skin Resident T Cell Interactions with NPY1R+ Neurons During Wound Repair Are Impaired by Obesity

Abstract

Wound repair involves complex cellular interactions to induce efficient healing. Skin resident {gamma}{delta} T cells regulate keratinocyte function and inflammatory responses in wound healing through the secretion of growth factors and cytokines. Some of these cytokines are involved in the neuroimmune axis, so we aimed to ascertain if {gamma}{delta} T cells and neurons exhibit crosstalk during wound repair. We identified a prevalent NPY1R+ peripheral neuron subset in the skin. {gamma}{delta} T cells interact with NPY1R+ neurons in the epidermis and dermis of both nonwounded and wounded murine skin. To determine the impact of the {gamma}{delta} TCR on NPY1R+ neuron interactions in wound healing, we compared epidermal T cell-neuron interactions in TCR{delta}-/- mice during wound repair. We found a decrease in interactions between epidermal {beta} T cells and NPY1R+ neurons in TCR{delta}-/- mice, suggesting {gamma}{delta} T cells communicate with NPY1R+ neurons more frequently than {beta} T cells in the epidermis, regardless of wound repair. In contrast, dermal T cell-neuron interactions in wildtype and TCR{delta}-/- mice during wound repair were similar between {beta} T cells and {gamma}{delta} T cells, suggesting both T cell types mediate communications with neurons in the dermis. In obese mice there are fewer NPY1R+ neurons and diminished neuron-T cell interactions indicative of neuropathy. Together these findings elucidate a neuroimmune crosstalk during wound repair that becomes disrupted in obesity.