Summary
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 Statement
The authors have declared no competing interest.
Footnotes
Abstract updated. Reformatting and changes to methods including additional information for antibody descriptions.
