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Association of synovial tissue polyfunctional T-cells with DAPSA in psoriatic arthritis

OBJECTIVE: This study examines polyfunctional T-cells in psoriatic arthritis (PsA) synovial tissue and their associations with clinical disease and implications for therapy. METHODS: PsA synovial tissue was enzymatically/mechanically digested to generate synovial tissue single cell suspensions. Freq...

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Autores principales: Wade, Sarah M, Canavan, Mary, McGarry, Trudy, Low, Candice, Wade, Siobhan C, Mullan, Ronan H, Veale, Douglas J, Fearon, Ursula
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6390025/
https://www.ncbi.nlm.nih.gov/pubmed/30626658
http://dx.doi.org/10.1136/annrheumdis-2018-214138
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author Wade, Sarah M
Canavan, Mary
McGarry, Trudy
Low, Candice
Wade, Siobhan C
Mullan, Ronan H
Veale, Douglas J
Fearon, Ursula
author_facet Wade, Sarah M
Canavan, Mary
McGarry, Trudy
Low, Candice
Wade, Siobhan C
Mullan, Ronan H
Veale, Douglas J
Fearon, Ursula
author_sort Wade, Sarah M
collection PubMed
description OBJECTIVE: This study examines polyfunctional T-cells in psoriatic arthritis (PsA) synovial tissue and their associations with clinical disease and implications for therapy. METHODS: PsA synovial tissue was enzymatically/mechanically digested to generate synovial tissue single cell suspensions. Frequencies of polyfunctional CD4, CD8, T-helper 1 (Th1), Th17 and exTh17 cells, using CD161 as a marker of Th17 plasticity, were determined by flow cytometry in matched PsA synovial tissue and peripheral blood. Synovial T-cell polyfunctionality was assessed in relation to Disease Activity in PSoriatic Arthritis (DAPSA) and in synovial cell suspensions cultured with a current mode of treatment, phosphodiesterase 4 (PDE4) inhibitor. RESULTS: PsA synovial tissue infiltrating CD4(+) T-cells expressed higher levels of interleukin (IL)-17A, interferon gamma (IFN-γ), GM-CSF and CD161, with parallel enrichment of Th1, Th17 and exTh17 T-helper subsets (all p<0.05). Interestingly, a significant proportion of synovial T-cell subsets were triple-positive for GM-CSF, tumour necrosis factor (-TNF), -IL-17 or IFN-γ compared with matched blood (all p<0.05). Importantly, frequencies of polyfunctional T-cells correlated with DAPSA: Th1-GM-CSF(+)/TNF(+)/IFN-γ(+) (r=0.7, p<0.01), Th17-GM-CSF(+)/TNF(+)/IL-17(+) (r=0.6, p<0.057) and exTh17-GM-CSF(+)/TNF(+)/IFN-γ(+) (r=0.7, p=0.0096), with no associations observed for single cytokine-producing T-cells. Following ex vivo culture of PsA synovial tissue cell suspensions, polyfunctional GM-CSF(+)TNFα(+)IL-17A(+) or/IFN-γ(+)-producing T-cells (p<0.05), but not single cytokine-producing T-cells, were inhibited with a PDE4 inhibitor. CONCLUSION: These data demonstrate enrichment of polyfunctional T-cells in PsA synovial tissue which were strongly associated with DAPSA and ex vivo therapeutic response.
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spelling pubmed-63900252019-03-12 Association of synovial tissue polyfunctional T-cells with DAPSA in psoriatic arthritis Wade, Sarah M Canavan, Mary McGarry, Trudy Low, Candice Wade, Siobhan C Mullan, Ronan H Veale, Douglas J Fearon, Ursula Ann Rheum Dis Psoriatic Arthritis OBJECTIVE: This study examines polyfunctional T-cells in psoriatic arthritis (PsA) synovial tissue and their associations with clinical disease and implications for therapy. METHODS: PsA synovial tissue was enzymatically/mechanically digested to generate synovial tissue single cell suspensions. Frequencies of polyfunctional CD4, CD8, T-helper 1 (Th1), Th17 and exTh17 cells, using CD161 as a marker of Th17 plasticity, were determined by flow cytometry in matched PsA synovial tissue and peripheral blood. Synovial T-cell polyfunctionality was assessed in relation to Disease Activity in PSoriatic Arthritis (DAPSA) and in synovial cell suspensions cultured with a current mode of treatment, phosphodiesterase 4 (PDE4) inhibitor. RESULTS: PsA synovial tissue infiltrating CD4(+) T-cells expressed higher levels of interleukin (IL)-17A, interferon gamma (IFN-γ), GM-CSF and CD161, with parallel enrichment of Th1, Th17 and exTh17 T-helper subsets (all p<0.05). Interestingly, a significant proportion of synovial T-cell subsets were triple-positive for GM-CSF, tumour necrosis factor (-TNF), -IL-17 or IFN-γ compared with matched blood (all p<0.05). Importantly, frequencies of polyfunctional T-cells correlated with DAPSA: Th1-GM-CSF(+)/TNF(+)/IFN-γ(+) (r=0.7, p<0.01), Th17-GM-CSF(+)/TNF(+)/IL-17(+) (r=0.6, p<0.057) and exTh17-GM-CSF(+)/TNF(+)/IFN-γ(+) (r=0.7, p=0.0096), with no associations observed for single cytokine-producing T-cells. Following ex vivo culture of PsA synovial tissue cell suspensions, polyfunctional GM-CSF(+)TNFα(+)IL-17A(+) or/IFN-γ(+)-producing T-cells (p<0.05), but not single cytokine-producing T-cells, were inhibited with a PDE4 inhibitor. CONCLUSION: These data demonstrate enrichment of polyfunctional T-cells in PsA synovial tissue which were strongly associated with DAPSA and ex vivo therapeutic response. BMJ Publishing Group 2019-03 2019-01-09 /pmc/articles/PMC6390025/ /pubmed/30626658 http://dx.doi.org/10.1136/annrheumdis-2018-214138 Text en © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Psoriatic Arthritis
Wade, Sarah M
Canavan, Mary
McGarry, Trudy
Low, Candice
Wade, Siobhan C
Mullan, Ronan H
Veale, Douglas J
Fearon, Ursula
Association of synovial tissue polyfunctional T-cells with DAPSA in psoriatic arthritis
title Association of synovial tissue polyfunctional T-cells with DAPSA in psoriatic arthritis
title_full Association of synovial tissue polyfunctional T-cells with DAPSA in psoriatic arthritis
title_fullStr Association of synovial tissue polyfunctional T-cells with DAPSA in psoriatic arthritis
title_full_unstemmed Association of synovial tissue polyfunctional T-cells with DAPSA in psoriatic arthritis
title_short Association of synovial tissue polyfunctional T-cells with DAPSA in psoriatic arthritis
title_sort association of synovial tissue polyfunctional t-cells with dapsa in psoriatic arthritis
topic Psoriatic Arthritis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6390025/
https://www.ncbi.nlm.nih.gov/pubmed/30626658
http://dx.doi.org/10.1136/annrheumdis-2018-214138
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