King's College London

Research portal

Polyfunctional, Proinflammatory, Tissue-Resident Memory Phenotype and Function of Synovial Interleukin-17A+CD8+ T Cells in Psoriatic Arthritis

Research output: Contribution to journalArticle

Standard

Polyfunctional, Proinflammatory, Tissue-Resident Memory Phenotype and Function of Synovial Interleukin-17A+CD8+ T Cells in Psoriatic Arthritis. / Steel, Kathryn J.A.; Srenathan, Ushani; Ridley, Michael; Durham, Lucy E.; Wu, Shih Ying; Ryan, Sarah E.; Hughes, Catherine D.; Chan, Estee; Kirkham, Bruce W.; Taams, Leonie S.

In: Arthritis and Rheumatology, Vol. 72, No. 3, 03.2020, p. 435-447.

Research output: Contribution to journalArticle

Harvard

Steel, KJA, Srenathan, U, Ridley, M, Durham, LE, Wu, SY, Ryan, SE, Hughes, CD, Chan, E, Kirkham, BW & Taams, LS 2020, 'Polyfunctional, Proinflammatory, Tissue-Resident Memory Phenotype and Function of Synovial Interleukin-17A+CD8+ T Cells in Psoriatic Arthritis', Arthritis and Rheumatology, vol. 72, no. 3, pp. 435-447. https://doi.org/10.1002/art.41156

APA

Steel, K. J. A., Srenathan, U., Ridley, M., Durham, L. E., Wu, S. Y., Ryan, S. E., ... Taams, L. S. (2020). Polyfunctional, Proinflammatory, Tissue-Resident Memory Phenotype and Function of Synovial Interleukin-17A+CD8+ T Cells in Psoriatic Arthritis. Arthritis and Rheumatology, 72(3), 435-447. https://doi.org/10.1002/art.41156

Vancouver

Steel KJA, Srenathan U, Ridley M, Durham LE, Wu SY, Ryan SE et al. Polyfunctional, Proinflammatory, Tissue-Resident Memory Phenotype and Function of Synovial Interleukin-17A+CD8+ T Cells in Psoriatic Arthritis. Arthritis and Rheumatology. 2020 Mar;72(3):435-447. https://doi.org/10.1002/art.41156

Author

Steel, Kathryn J.A. ; Srenathan, Ushani ; Ridley, Michael ; Durham, Lucy E. ; Wu, Shih Ying ; Ryan, Sarah E. ; Hughes, Catherine D. ; Chan, Estee ; Kirkham, Bruce W. ; Taams, Leonie S. / Polyfunctional, Proinflammatory, Tissue-Resident Memory Phenotype and Function of Synovial Interleukin-17A+CD8+ T Cells in Psoriatic Arthritis. In: Arthritis and Rheumatology. 2020 ; Vol. 72, No. 3. pp. 435-447.

Bibtex Download

@article{9d472af7866a49edaf267ae848704300,
title = "Polyfunctional, Proinflammatory, Tissue-Resident Memory Phenotype and Function of Synovial Interleukin-17A+CD8+ T Cells in Psoriatic Arthritis",
abstract = "Objective: Genetic associations imply a role for CD8+ T cells and the interleukin-23 (IL-23)/IL-17 axis in psoriatic arthritis (PsA) and other spondyloarthritides (SpA). IL-17A+CD8+ (Tc17) T cells are enriched in the synovial fluid (SF) of patients with PsA, and IL-17A blockade is clinically efficacious in PsA/SpA. This study was undertaken to determine the immunophenotype, molecular profile, and function of synovial Tc17 cells in order to elucidate their role in PsA/SpA pathogenesis. Methods: Peripheral blood (PB) and SF mononuclear cells were isolated from patients with PsA or other types of SpA. Cells were phenotypically, transcriptionally, and functionally analyzed by flow cytometry (n = 6–18), T cell receptor β (TCRβ) sequencing (n = 3), RNA-Seq (n = 3), quantitative reverse transcriptase–polymerase chain reaction (n = 4), and Luminex or enzyme-linked immunosorbent assay (n = 4–16). Results: IL-17A+CD8+ T cells were predominantly TCRαβ+ and their frequencies were increased in the SF versus the PB of patients with established PsA (P < 0.0001) or other SpA (P = 0.0009). TCRβ sequencing showed that these cells were polyclonal in PsA (median clonality 0.08), while RNA-Seq and deep immunophenotyping revealed that PsA synovial Tc17 cells had hallmarks of Th17 cells (RORC/IL23R/CCR6/CD161) and Tc1 cells (granzyme A/B). Synovial Tc17 cells showed a strong tissue-resident memory T (Trm) cell signature and secreted a range of proinflammatory cytokines. We identified CXCR6 as a marker for synovial Tc17 cells, and increased levels of CXCR6 ligand CXCL16 in PsA SF (P = 0.0005), which may contribute to their retention in the joint. Conclusion: Our results identify synovial Tc17 cells as a polyclonal subset of Trm cells characterized by polyfunctional, proinflammatory mediator production and CXCR6 expression. The molecular signature and functional profiling of these cells may help explain how Tc17 cells can contribute to synovial inflammation and disease persistence in PsA and possibly other types of SpA.",
author = "Steel, {Kathryn J.A.} and Ushani Srenathan and Michael Ridley and Durham, {Lucy E.} and Wu, {Shih Ying} and Ryan, {Sarah E.} and Hughes, {Catherine D.} and Estee Chan and Kirkham, {Bruce W.} and Taams, {Leonie S.}",
year = "2020",
month = "3",
doi = "10.1002/art.41156",
language = "English",
volume = "72",
pages = "435--447",
journal = "Arthritis and Rheumatology",
issn = "2326-5191",
number = "3",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - Polyfunctional, Proinflammatory, Tissue-Resident Memory Phenotype and Function of Synovial Interleukin-17A+CD8+ T Cells in Psoriatic Arthritis

AU - Steel, Kathryn J.A.

AU - Srenathan, Ushani

AU - Ridley, Michael

AU - Durham, Lucy E.

AU - Wu, Shih Ying

AU - Ryan, Sarah E.

AU - Hughes, Catherine D.

AU - Chan, Estee

AU - Kirkham, Bruce W.

AU - Taams, Leonie S.

PY - 2020/3

Y1 - 2020/3

N2 - Objective: Genetic associations imply a role for CD8+ T cells and the interleukin-23 (IL-23)/IL-17 axis in psoriatic arthritis (PsA) and other spondyloarthritides (SpA). IL-17A+CD8+ (Tc17) T cells are enriched in the synovial fluid (SF) of patients with PsA, and IL-17A blockade is clinically efficacious in PsA/SpA. This study was undertaken to determine the immunophenotype, molecular profile, and function of synovial Tc17 cells in order to elucidate their role in PsA/SpA pathogenesis. Methods: Peripheral blood (PB) and SF mononuclear cells were isolated from patients with PsA or other types of SpA. Cells were phenotypically, transcriptionally, and functionally analyzed by flow cytometry (n = 6–18), T cell receptor β (TCRβ) sequencing (n = 3), RNA-Seq (n = 3), quantitative reverse transcriptase–polymerase chain reaction (n = 4), and Luminex or enzyme-linked immunosorbent assay (n = 4–16). Results: IL-17A+CD8+ T cells were predominantly TCRαβ+ and their frequencies were increased in the SF versus the PB of patients with established PsA (P < 0.0001) or other SpA (P = 0.0009). TCRβ sequencing showed that these cells were polyclonal in PsA (median clonality 0.08), while RNA-Seq and deep immunophenotyping revealed that PsA synovial Tc17 cells had hallmarks of Th17 cells (RORC/IL23R/CCR6/CD161) and Tc1 cells (granzyme A/B). Synovial Tc17 cells showed a strong tissue-resident memory T (Trm) cell signature and secreted a range of proinflammatory cytokines. We identified CXCR6 as a marker for synovial Tc17 cells, and increased levels of CXCR6 ligand CXCL16 in PsA SF (P = 0.0005), which may contribute to their retention in the joint. Conclusion: Our results identify synovial Tc17 cells as a polyclonal subset of Trm cells characterized by polyfunctional, proinflammatory mediator production and CXCR6 expression. The molecular signature and functional profiling of these cells may help explain how Tc17 cells can contribute to synovial inflammation and disease persistence in PsA and possibly other types of SpA.

AB - Objective: Genetic associations imply a role for CD8+ T cells and the interleukin-23 (IL-23)/IL-17 axis in psoriatic arthritis (PsA) and other spondyloarthritides (SpA). IL-17A+CD8+ (Tc17) T cells are enriched in the synovial fluid (SF) of patients with PsA, and IL-17A blockade is clinically efficacious in PsA/SpA. This study was undertaken to determine the immunophenotype, molecular profile, and function of synovial Tc17 cells in order to elucidate their role in PsA/SpA pathogenesis. Methods: Peripheral blood (PB) and SF mononuclear cells were isolated from patients with PsA or other types of SpA. Cells were phenotypically, transcriptionally, and functionally analyzed by flow cytometry (n = 6–18), T cell receptor β (TCRβ) sequencing (n = 3), RNA-Seq (n = 3), quantitative reverse transcriptase–polymerase chain reaction (n = 4), and Luminex or enzyme-linked immunosorbent assay (n = 4–16). Results: IL-17A+CD8+ T cells were predominantly TCRαβ+ and their frequencies were increased in the SF versus the PB of patients with established PsA (P < 0.0001) or other SpA (P = 0.0009). TCRβ sequencing showed that these cells were polyclonal in PsA (median clonality 0.08), while RNA-Seq and deep immunophenotyping revealed that PsA synovial Tc17 cells had hallmarks of Th17 cells (RORC/IL23R/CCR6/CD161) and Tc1 cells (granzyme A/B). Synovial Tc17 cells showed a strong tissue-resident memory T (Trm) cell signature and secreted a range of proinflammatory cytokines. We identified CXCR6 as a marker for synovial Tc17 cells, and increased levels of CXCR6 ligand CXCL16 in PsA SF (P = 0.0005), which may contribute to their retention in the joint. Conclusion: Our results identify synovial Tc17 cells as a polyclonal subset of Trm cells characterized by polyfunctional, proinflammatory mediator production and CXCR6 expression. The molecular signature and functional profiling of these cells may help explain how Tc17 cells can contribute to synovial inflammation and disease persistence in PsA and possibly other types of SpA.

UR - http://www.scopus.com/inward/record.url?scp=85077879586&partnerID=8YFLogxK

U2 - 10.1002/art.41156

DO - 10.1002/art.41156

M3 - Article

C2 - 31677365

AN - SCOPUS:85077879586

VL - 72

SP - 435

EP - 447

JO - Arthritis and Rheumatology

JF - Arthritis and Rheumatology

SN - 2326-5191

IS - 3

ER -

View graph of relations

© 2018 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454