Identification of Functional Subsets within Epidermal γδ T Cells in Imiquimod-induced Psoriasis 2259187

Abstract Introduction Approximately 3% of Americans suffer from psoriasis, an autoimmune skin disorder that causes inflamed lesions on the skin. Psoriasis pathogenesis involves a complex interplay between a variety of immune cell types, including skin-resident T cells. We have recently shown that a subset of CCR6+ epidermal γδ T cells produce IL-17 during psoriasis; however, the function of other epidermal γδ T cell subsets in disease remains unknown. We have identified and characterized five distinct functional subsets of epidermal γδ T cells in a murine model of imiquimod (IMQ)-induced psoriasis. Reanalysis of single-cell RNA sequencing data from IMQ-treated mice identifies five transcriptionally distinct epidermal γδ T cell subsets with separate functions. We have defined these subsets as: Th1, neuronal, regulatory, proliferative, and Th17. We further characterized these subsets in IMQ-induced psoriasis using immunofluorescent microscopy and flow cytometry to quantify the populations and interrogate their function. Elucidating functional epidermal γδ T cell populations in psoriasis provides a deeper understanding of skin immune regulation and the identification of potential therapeutic targets for psoriasis and related skin inflammation. Methods Epidermal sheets were isolated from imiquimod-treated murine ears, stained with γδTCR-APC, CD94-FITC, and CD24-PE, and imaged using immunofluorescence microscopy to identify and quantify functional γδ T cell subsets. Results Immunofluorescence imaging revealed epidermal γδ T cells co-expressing γγTCR-APC and CD24-PE during imiquimod-induced inflammation. Conclusion These findings suggest that distinct epidermal γδ T cell populations can be identified by CD24 expression, providing insight into their potential roles in cutaneous immune responses. Funding Source Beckman Scholars Program Topic Categories Innate Immune Responses and Host Defense: Molecular Mechanisms (INM)