Resident T Cells in Resolved Psoriasis Steer Tissue Responses that Stratify Clinical Outcome

• Published in: Journal of investigative dermatology Vol. 138; no. 8; pp. 1754 - 1763
• Main Authors: Gallais Sérézal, Irène, Classon, Cajsa, Cheuk, Stanley, Barrientos-Somarribas, Mauricio, Wadman, Emma, Martini, Elisa, Chang, David, Xu Landén, Ning, Ehrström, Marcus, Nylén, Susanne, Eidsmo, Liv
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2018
• Subjects: Aged; beta-Defensins - immunology; beta-Defensins - metabolism; Biopsy; Cells, Cultured; Female; Follow-Up Studies; Gene Expression Profiling; Humans; Immunologic Memory - radiation effects; Interleukin-17 - immunology; Interleukin-17 - metabolism; Keratinocytes - immunology; Keratinocytes - radiation effects; Lymphocyte Activation - radiation effects; Male; Medicin och hälsovetenskap; Middle Aged; Muromonab-CD3 - immunology; Psoriasis - immunology; Psoriasis - pathology; Psoriasis - radiotherapy; Recurrence; Sequence Analysis, RNA; Skin - cytology; Skin - immunology; Skin - pathology; Skin - radiation effects; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - radiation effects; Tissue Culture Techniques; Treatment Outcome; Ultraviolet Therapy - methods; TRM; DEG
• ISSN: 0022-202X; 1523-1747; 1523-1747
• DOI: 10.1016/j.jid.2018.02.030

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.