Research & Innovation
Publications
T Cells Promote Distinct Transcriptional Programs of Cutaneous Inflammatory Disease in Keratinocytes and Dermal Fibroblasts
PMU Author
Iris K. Gratz
All Authors
Hannah A. DeBerg, Mitch L. Fahning, Suraj R. Varkhande, James D. Schlenker, William P. Schmitt, Aayush Gupta, Archana Singh, Iris K. Gratz, Jeffrey S. Carlin, Daniel J. Campbell, Peter A. Morawski
Journal association
JOURNAL OF INVESTIGATIVE DERMATOLOGY
Abstract
T cells and structural cells coordinate appropriate inflammatory responses and restoration of barrier integrity following insult. Dysfunctional T cells precipitate skin pathology occurring alongside altered structural cell frequencies and transcriptional states, but to what extent different T cells promote disease-associated changes remains unclear. We show that functionally diverse circulating and skin-resident CD4+CLA+ T-cell populations promote distinct transcriptional outcomes in human keratinocytes and fibroblasts associated with inflamed or healthy tissue. We identify T helper 17 cell-induced genes in keratinocytes that are enriched in psoriasis patient skin and normalized by anti-IL-17 therapy. We also describe a CD103+ skin-resident T-cell-induced transcriptional module enriched in healthy controls that is diminished during psoriasis and scleroderma and show that CD103+ T-cell frequencies are altered during disease. Interrogating clinical data using immune-dependent transcriptional signatures defines the T-cell subsets and genes distinguishing inflamed from healthy skin and allows investigation of heterogeneous patient responses to biologic therapy.
Keywords
SKIN INFLAMMATION, PSORIASIS, Atopic dermatitis, CD4 T cells, Scleroderma