
==== Front
bioRxiv
BIORXIV
bioRxiv
2692-8205
Cold Spring Harbor Laboratory

39131334
10.1101/2024.07.31.606077
preprint
3
Article
T cells promote distinct transcriptional programs of cutaneous inflammatory disease in human skin structural cells
DeBerg Hannah A http://orcid.org/0000-0002-5263-158X

Fahning Mitch L http://orcid.org/0000-0001-9352-4409

Schlenker James D
Schmitt William P
Gratz Iris K http://orcid.org/0000-0001-7470-7277

Carlin Jeffrey S http://orcid.org/0009-0006-5634-1981

Campbell Daniel J http://orcid.org/0000-0002-9652-7178

Morawski Peter A http://orcid.org/0000-0001-9159-4032

31 8 2024
2024.07.31.606077https://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
http://biorxiv.org/lookup/doi/10.1101/2024.07.31.606077
nihpp-2024.07.31.606077.pdf
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.
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pmc
