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Tissue-Resident Memory CD8+ T Cells From Skin Differentiate Psoriatic Arthritis From Psoriasis.
- Source :
-
Arthritis & rheumatology (Hoboken, N.J.) [Arthritis Rheumatol] 2021 Jul; Vol. 73 (7), pp. 1220-1232. Date of Electronic Publication: 2021 May 25. - Publication Year :
- 2021
-
Abstract
- Objective: To compare immune cell phenotype and function in psoriatic arthritis (PsA) versus psoriasis in order to better understand the pathogenesis of PsA.<br />Methods: In-depth immunophenotyping of different T cell and dendritic cell subsets was performed in patients with PsA, psoriasis, or axial spondyloarthritis and healthy controls. Subsequently, we analyzed cells from peripheral blood, synovial fluid (SF), and skin biopsy specimens using flow cytometry, along with high-throughput transcriptome analyses and functional assays on the specific cell populations that appeared to differentiate PsA from psoriasis.<br />Results: Compared to healthy controls, the peripheral blood of patients with PsA was characterized by an increase in regulatory CD4+ T cells and interleukin-17A (IL-17A) and IL-22 coproducing CD8+ T cells. One population specifically differentiated PsA from psoriasis: i.e., CD8+CCR10+ T cells were enriched in PsA. CD8+CCR10+ T cells expressed high levels of DNAX accessory molecule 1 and were effector memory cells that coexpressed skin-homing receptors CCR4 and cutaneous lymphocyte antigen. CD8+CCR10+ T cells were detected under inflammatory and homeostatic conditions in skin, but were not enriched in SF. Gene profiling further revealed that CD8+CCR10+ T cells expressed GATA3, FOXP3, and core transcriptional signature of tissue-resident memory T cells, including CD103. Specific genes, including RORC, IFNAR1, and ERAP1, were up-regulated in PsA compared to psoriasis. CD8+CCR10+ T cells were endowed with a Tc2/22-like cytokine profile, lacked cytotoxic potential, and displayed overall regulatory function.<br />Conclusion: Tissue-resident memory CD8+ T cells derived from the skin are enhanced in the circulation of patients with PsA compared to patients with psoriasis alone. This may indicate that aberrances in cutaneous tissue homeostasis contribute to arthritis development.<br /> (© 2021 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)
- Subjects :
- Adult
Aminopeptidases genetics
Antigens, CD genetics
Antigens, Differentiation, T-Lymphocyte immunology
Arthritis, Psoriatic genetics
Arthritis, Psoriatic pathology
CD8-Positive T-Lymphocytes metabolism
Case-Control Studies
Female
Forkhead Transcription Factors genetics
GATA3 Transcription Factor genetics
Gene Expression Profiling
High-Throughput Nucleotide Sequencing
Humans
Immunologic Memory immunology
Immunophenotyping
Integrin alpha Chains genetics
Interleukin-17 immunology
Interleukins immunology
Male
Middle Aged
Minor Histocompatibility Antigens genetics
Nuclear Receptor Subfamily 1, Group F, Member 3 genetics
Oligosaccharides metabolism
Psoriasis genetics
Psoriasis pathology
Receptor, Interferon alpha-beta genetics
Receptors, CCR10 metabolism
Receptors, CCR4 metabolism
Sialyl Lewis X Antigen analogs & derivatives
Sialyl Lewis X Antigen metabolism
Skin pathology
Spondylarthropathies genetics
Spondylarthropathies immunology
Spondylarthropathies pathology
Synovial Fluid cytology
T-Lymphocyte Subsets metabolism
T-Lymphocytes, Cytotoxic immunology
T-Lymphocytes, Regulatory metabolism
Interleukin-22
Arthritis, Psoriatic immunology
CD8-Positive T-Lymphocytes immunology
Psoriasis immunology
Skin immunology
T-Lymphocyte Subsets immunology
T-Lymphocytes, Regulatory immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2326-5205
- Volume :
- 73
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Arthritis & rheumatology (Hoboken, N.J.)
- Publication Type :
- Academic Journal
- Accession number :
- 33452865
- Full Text :
- https://doi.org/10.1002/art.41652