PT - JOURNAL ARTICLE AU - DeBerg, Hannah A. AU - Fahning, Mitch L. AU - Schlenker, James D. AU - Schmitt, William P. AU - Gratz, Iris K. AU - Carlin, Jeffrey S. AU - Campbell, Daniel J. AU - Morawski, Peter A. TI - T cells promote distinct transcriptional programs of cutaneous inflammatory disease in human skin structural cells AID - 10.1101/2024.07.31.606077 DP - 2024 Jan 01 TA - bioRxiv PG - 2024.07.31.606077 4099 - http://biorxiv.org/content/early/2024/08/15/2024.07.31.606077.short 4100 - http://biorxiv.org/content/early/2024/08/15/2024.07.31.606077.full AB - T cells and structural cells coordinate appropriate inflammatory responses and restoration of barrier integrity following insult. Dysfunctional T cell activity precipitates tissue pathology that occurs alongside disease- associated alterations of structural cell subsets, but the mechanisms by which T cells promote these changes remain unclear. We show that subsets of circulating and skin-resident CD4+ T cells promote distinct transcriptional outcomes in human keratinocytes and dermal fibroblasts that correspond with divergent T cell cytokine production. Using these transcriptional signatures, we identify T cell-dependent outcomes associated with inflammatory skin disease, including a set of Th17 cell-induced genes in keratinocytes that are enriched in the skin during psoriasis and normalized by anti-IL-17 therapy, and a skin- resident T cell-induced gene module enriched in scleroderma-associated fibroblasts. Interrogating clinical data using T cell-derived structural cell gene networks enables investigation of the immune-dependent contribution to inflammatory disease and the heterogeneous patient response to biologic therapy.Competing Interest StatementThe authors have declared no competing interest.