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bioRxiv · 10.1101/2024.04.09.588780

Impact of Obesity on the CCR6-CCL20 Axis in Epidermal γδ T Cells and IL-17A Production in Murine Wound Healing and Psoriasis

Lawler, W.·Castellanos, T.·Engel, E.·Alvizo, C.·Kasler, A.·Bshara-Corson, S.·Jameson, J.
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Abstract

Obesity is associated with comorbidities including type 2 diabetes, chronic nonhealing wounds and psoriasis. Normally skin homeostasis and repair is regulated through the production of cytokines and growth factors derived from skin-resident cells including epidermal {gamma}{delta} T cells. However epidermal {gamma}{delta} T cells exhibit reduced proliferation and defective growth factor and cytokine production during obesity and type 2 diabetes. One of the genes modulated in epidermal {gamma}{delta} T cells during obesity and type 2 diabetes is CCR6, which is the receptor for CCL20. CCL20 is elevated in the skin during obesity and type 2 diabetes. Here we identify a subset of murine epidermal {gamma}{delta} T cells that expresses CCR6 in response to activation in vitro and post-wounding or psoriasis induction with imiquimod in vivo. We show that CCL20 stimulates epidermal {gamma}{delta} T cells to produce IL-17 suggesting CCR6 regulates the IL-17 axis as in dermal {gamma}{delta} T cells. Further, epidermal {gamma}{delta} T cells upregulate CCR6 and produce IL-17 during murine models of wound repair and psoriasis. Obesity increases CCR6 and IL-17 expression by epidermal {gamma}{delta} T cells during wound repair but has less of an effect during psoriasis. These findings have novel implications for the regulation of a specific population of IL-17-producing epidermal {gamma}{delta} T cells during skin damage and inflammation.

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Lawler, W., Castellanos, T., Engel, E., Alvizo, C., Kasler, A., Bshara-Corson, S., Jameson, J.. 2024-04-13. Impact of Obesity on the CCR6-CCL20 Axis in Epidermal γδ T Cells and IL-17A Production in Murine Wound Healing and Psoriasis. https://doi.org/10.1101/2024.04.09.588780

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