Resident T Cells in Resolved Psoriasis Steer Tissue Responses that Stratify Clinical Outcome.
Irène Gallais Sérézal, Cajsa Classon, Stanley Cheuk, Mauricio Barrientos-Somarribas, Emma Wadman, Elisa Martini, David Chang, Ning Xu Landén, Marcus Ehrström, Susanne Nylén, Liv Eidsmo
Author Information
Irène Gallais Sérézal: Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Department of Dermatology, Karolinska University Hospital, Stockholm, Sweden.
Cajsa Classon: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Stanley Cheuk: Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Mauricio Barrientos-Somarribas: Department of Cell and Molecular Biology Karolinska Institutet, Stockholm, Sweden.
Emma Wadman: Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Elisa Martini: Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Department of Dermatology, Karolinska University Hospital, Stockholm, Sweden.
David Chang: Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Ning Xu Landén: Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Department of Dermatology, Karolinska University Hospital, Stockholm, Sweden.
Marcus Ehrström: Department of Reconstructive Plastic Surgery, Karolinska University Hospital Solna, Stockholm, Sweden.
Susanne Nylén: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Liv Eidsmo: Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Department of Dermatology, Karolinska University Hospital, Stockholm, Sweden. Electronic address: liv.eidsmo@ki.se.
Psoriasis is driven by focal disruptions of the immune-homeostasis in human skin. Local relapse following cessation of therapy is common and unpredictable, which complicates clinical management of psoriasis. We have previously shown that pathogenic resident T cells accumulate in active and resolved psoriasis, but whether these cells drive psoriasiform tissue reactions is less clear. Here, we activated T cells within skin explants using the pan-T cell activating antibody OKT-3. To explore if T cells induced different tissue response patterns in healthy and psoriasis afflicted skin, transcriptomic analyses were performed with RNA-sequencing and Nanostring. Core tissue responses dominated by IFN-induced pathways were triggered regardless of the inflammatory status of the skin. In contrast, pathways induced by IL-17A, including Defensin beta 2 and keratinocyte differentiation markers, were activated in psoriasis samples. An integrated analysis of IL-17A and IFN-related responses revealed that IL-17 dominated tissue response correlated with early relapse following UVB treatment. Stratification of tissue responses to T cell activation in resolved lesions could potentially offer individualized prediction of disease relapse during long-term immunomodulatory treatment.
