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Tissue‐Resident Memory CD8+ T Cells From Skin Differentiate Psoriatic Arthritis From Psoriasis
Author(s) -
Leijten Emmerik F.,
Kempen Tessa S.,
Olde Nordkamp Michel A.,
Pouw Juliette N.,
Kleinrensink Nienke J.,
Vincken Nanette L.,
Mertens Jorre,
Balak Deepak M. W.,
Verhagen Fleurieke H.,
Hartgring Sarita A.,
Lubberts Erik,
Tekstra Janneke,
Pandit Aridaman,
Radstake Timothy R.,
Boes Marianne
Publication year - 2021
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.41652
Subject(s) - cytotoxic t cell , immunology , psoriasis , cd8 , foxp3 , gata3 , il 2 receptor , t cell , medicine , biology , immune system , transcription factor , biochemistry , gene , in vitro
Objective To compare immune cell phenotype and function in psoriatic arthritis (PsA) versus psoriasis in order to better understand the pathogenesis of PsA. 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. 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. 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.