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

Wound repair involves complex cellular interactions to induce efficient healing. Skin resident γδ 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 γδ T cells and neurons exhibit crosstalk during wound repair. We identified a prevalent NPY1R ⁺ peripheral neuron subset in the skin. γδ T cells interact with NPY1R ⁺ neurons in the epidermis and dermis of both nonwounded and wounded murine skin. To determine the impact of the γδ TCR on NPY1R ⁺ neuron interactions in wound healing, we compared epidermal T cell-neuron interactions in TCRδ ^−/− mice during wound repair. We found a decrease in interactions between epidermal αβ T cells and NPY1R ⁺ neurons in TCRδ ^−/− mice, suggesting γδ T cells communicate with NPY1R ⁺ neurons more frequently than αβ T cells in the epidermis, regardless of wound repair. In contrast, dermal T cell-neuron interactions in wildtype and TCRδ ^−/− mice during wound repair were similar between αβ T cells and γδ 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.