Abstract
T cells coordinate with structural cells in the skin to promote appropriate inflammatory responses and subsequent restoration of barrier integrity following insult. Gene expression studies cataloging human skin have defined transcriptionally distinct structural cell populations in healthy tissue and identified inflammatory disease-associated changes in epithelial keratinocytes and dermal fibroblasts. Cutaneous T lymphocyte activity is implicated in the development of inflammatory skin disease, but the mechanisms by which T cells promote disease-associated changes in the skin remain unclear. We show that subsets of circulating and skin-resident CD4+ T cells promote distinct transcriptional outcomes in human keratinocytes and fibroblasts. Using these in vitro generated transcriptional signatures, we identify T cell-dependent gene modules associated with inflammatory skin diseases in vivo, such as a set of Th17 cell-induced genes in keratinocytes that are enriched in the skin of patients with psoriasis and normalized in response to anti-IL-17 therapy. Interrogating clinical trial findings using in vitro generated structural cell gene networks enables investigation of the immune-dependent contribution to inflammatory skin disease and the heterogeneous patient response to biologic therapy.
Competing Interest Statement
The authors have declared no competing interest.
