Tulloch, P. | Search bioRxiv

bioRxiv2025

TNFR2 is Expressed by a Discrete Subset of Epidermal γ δ T Cells with an IL-17 Gene Signature during Psoriasis

Psoriasis is a chronic skin disease that results in scaly patches and affects 2-3% of people worldwide. Therapeutic treatment targets the TNF-/IL-17 axis to disrupt keratinocyte hyperproliferation and inflammation. While more is known about the role of dermal {beta} and {gamma}{delta} T cells in IL-17 production, less is understood about the role of resident epidermal T cells. Here, we examine how TNF- modulates epidermal {gamma}{delta} T cell activation and function. We show that a subset of activated epidermal {gamma}{delta} T cells expresses TNFR2 with or without TNFR1. Stimulation with TNF- induces epidermal {gamma}{delta} T cells to produce IL-17 family cytokines and chemokines. Epidermal {gamma}{delta} T cells do not require TNFR1 or 2 for development or homing to the skin. Instead, TNFR2 plays roles in epidermal {gamma}{delta} T cell function skewing them toward a T{gamma}{delta}17 phenotype during psoriasis. Investigation of the mechanisms by which TNF- associated inflammation impacts epidermal {gamma}{delta} T cell function may help identify new cellular targets for immunotherapy or mark them as early regulators of skin inflammation.

immunology↗

bioRxiv2025

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 {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.

immunology↗