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Resident T Cells in Resolved Psoriasis Steer Tissue Responses that Stratify Clinical Outcome
- Source :
- Journal of Investigative Dermatology. 138:1754-1763
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- 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.
- Subjects :
- Keratinocytes
Male
0301 basic medicine
beta-Defensins
Biopsy
T cell
Cell
Human skin
Dermatology
Lymphocyte Activation
Biochemistry
Tissue Culture Techniques
Transcriptome
03 medical and health sciences
Recurrence
T-Lymphocyte Subsets
Psoriasis
Humans
Medicine
Molecular Biology
Cells, Cultured
Aged
Skin
integumentary system
medicine.diagnostic_test
biology
Sequence Analysis, RNA
business.industry
Gene Expression Profiling
Interleukin-17
Cell Biology
Middle Aged
medicine.disease
Gene expression profiling
Treatment Outcome
030104 developmental biology
medicine.anatomical_structure
Immunology
biology.protein
Female
Ultraviolet Therapy
Antibody
business
Immunologic Memory
Follow-Up Studies
Muromonab-CD3
Subjects
Details
- ISSN :
- 0022202X
- Volume :
- 138
- Database :
- OpenAIRE
- Journal :
- Journal of Investigative Dermatology
- Accession number :
- edsair.doi.dedup.....5f158b40c11b18e688d0fed1d4fb4027