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bioRxiv · 10.1101/2025.09.05.674535

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

Ahmed, J.·Matthews, C.·Tulloch, P.·Lawler, W.·Mendoza, A.·Rhoiney, M.·Jameson, J.
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Abstract

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.

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Ahmed, J., Matthews, C., Tulloch, P., Lawler, W., Mendoza, A., Rhoiney, M., Jameson, J.. 2025-09-10. TNFR2 is Expressed by a Discrete Subset of Epidermal γ δ T Cells with an IL-17 Gene Signature during Psoriasis. https://doi.org/10.1101/2025.09.05.674535

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