TY - JOUR
T1 - Tissue-resident memory CD8+ T cells from skin differentiate psoriatic arthritis from psoriasis
AU - Leijten, Emmerik F
AU - van Kempen, Tessa S
AU - Olde Nordkamp, Michel A
AU - Pouw, Juliette N
AU - Kleinrensink, Nienke J
AU - Vincken, Nanette L
AU - Mertens, Jorre
AU - Balak, Deepak M W
AU - Verhagen, Fleurieke H
AU - Hartgring, Sarita A
AU - Lubberts, Erik
AU - Tekstra, Janneke
AU - Pandit, Aridaman
AU - Radstake, Timothy R
AU - Boes, Marianne
N1 - Funding Information:
We thank the patients for their participation in the study, the clinical study team (Anne Karien Marijnissen, Anneloes van Loo, Karin Schrijvers, and Joke Nijdeken), and the flow core facility of the Center for Translational Immunology. We also thank Jonas Kuipers for his scientific input.
Publisher Copyright:
© 2021 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.
PY - 2021/7
Y1 - 2021/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85106293004&partnerID=8YFLogxK
U2 - 10.1002/art.41652
DO - 10.1002/art.41652
M3 - Article
C2 - 33452865
SN - 2326-5191
VL - 73
SP - 1220
EP - 1232
JO - Arthritis & Rheumatology
JF - Arthritis & Rheumatology
IS - 7
ER -