{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T22:10:54Z","timestamp":1780956654057,"version":"3.54.1"},"reference-count":42,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2020,7,8]],"date-time":"2020-07-08T00:00:00Z","timestamp":1594166400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Reumafonds","award":["Novartis research grant"],"award-info":[{"award-number":["Novartis research grant"]}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis & Rheumatology"],"published-print":{"date-parts":[[2020,8]]},"abstract":"Objective<\/jats:title>Interleukin\u201017A (IL<\/jats:styled-content>\u201017A) and tumor necrosis factor (TNF<\/jats:styled-content>) contribute to the pathogenesis of psoriatic arthritis (PsA). However, their functional relationship in PsA synovitis has not been fully elucidated. Additionally, although CD<\/jats:styled-content>8+ T cells in PsA have been recognized via flow cytometry as a source of IL<\/jats:styled-content>\u201017A production, it is not clear whether CD<\/jats:styled-content>8+ T cells secrete IL<\/jats:styled-content>\u201017A under more physiologically relevant conditions in the context from PsA synovitis. This study was undertaken to clarify the roles of IL<\/jats:styled-content>\u201017A and TNF<\/jats:styled-content> in the synovial fluid (SF<\/jats:styled-content>) from patients with PsA and investigate the impact of CD<\/jats:styled-content>8+ T cells on IL<\/jats:styled-content>\u201017A production.<\/jats:p><\/jats:sec>Methods<\/jats:title>IL<\/jats:styled-content>\u201017A+ T cells were identified by flow cytometry in SF<\/jats:styled-content> samples from 20 patients with active PsA, blood samples from 22 treatment\u2010naive patients with PsA, and blood samples from 22 healthy donors. IL<\/jats:styled-content>\u201017A+ T cells were sorted from 12 PsA SF<\/jats:styled-content> samples and stimulated using anti\u2010CD<\/jats:styled-content>3\/anti\u2010CD<\/jats:styled-content>28 or phorbol myristate acetate (PMA<\/jats:styled-content>) and ionomycin ex vivo, alone (n = 3) or together with autologous monocytes (n = 3) or PsA fibroblast\u2010like synoviocytes (FLS<\/jats:styled-content>) (n = 5\u20136). To evaluate the differential allogeneic effects of neutralizing IL<\/jats:styled-content>\u201017A and TNF<\/jats:styled-content>, SF CD<\/jats:styled-content>4+ T cells and PsA FLS<\/jats:styled-content> cocultures were also used (n = 5\u20136).<\/jats:p><\/jats:sec>Results<\/jats:title>Flow cytometry analyses of SF<\/jats:styled-content> samples from patients with PsA showed IL\u201017A positivity for CD<\/jats:styled-content>4+ and CD<\/jats:styled-content>8+ T cells (IL<\/jats:styled-content>\u201017A, median 0.71% [interquartile range 0.35\u20131.50%] in CD<\/jats:styled-content>4+ cells; median 0.44% [interquartile range 0.17\u20131.86%] in CD<\/jats:styled-content>8+ T cells).<\/jats:p>However, only CD<\/jats:styled-content>4+ T cells secreted IL<\/jats:styled-content>\u201017A after anti\u2010CD<\/jats:styled-content>3\/anti\u2010CD<\/jats:styled-content>28 activation, when cultured alone and in cocultures with PsA monocytes or PsA FLS<\/jats:styled-content> (each P<\/jats:italic> < 0.05). Remarkably, CD<\/jats:styled-content>8+ T cells only secreted IL<\/jats:styled-content>\u201017A after 4\u2010 or 72\u2010hour stimulation with PMA<\/jats:styled-content>\/ionomycin. Anti\u2013IL<\/jats:styled-content>\u201017A and anti\u2010TNF<\/jats:styled-content> treatments both inhibited PsA synovitis ex vivo. Neutralizing IL<\/jats:styled-content>\u201017A strongly inhibited IL<\/jats:styled-content>\u20106 (P<\/jats:italic> < 0.05) and IL<\/jats:styled-content>\u20101\u03b2 (P<\/jats:italic> < 0.01), while anti\u2010TNF<\/jats:styled-content> treatment was more potent in reducing matrix metalloproteinase 3 (MMP<\/jats:styled-content>\u20103) (P<\/jats:italic> < 0.05) and MMP<\/jats:styled-content>\u201013.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>CD<\/jats:styled-content>8+ T cells, in contrast to CD<\/jats:styled-content>4+ T cells, in SF<\/jats:styled-content> specimens obtained from PsA patients did not secrete IL<\/jats:styled-content>\u201017A following T cell receptor activation. Overlapping, but distinct, effects at the level of inflammatory cytokines and MMP<\/jats:styled-content>s were found after neutralizing IL<\/jats:styled-content>\u201017A or TNF<\/jats:styled-content> ex vivo in a human model of PsA synovitis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.41271","type":"journal-article","created":{"date-parts":[[2020,4,3]],"date-time":"2020-04-03T12:21:31Z","timestamp":1585916491000},"page":"1303-1313","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Interleukin\u201017A Is Produced by CD4+ but Not CD8+ T Cells in Synovial Fluid Following T Cell Receptor Activation and Regulates Different Inflammatory Mediators Compared to Tumor Necrosis Factor in a Model of Psoriatic Arthritis Synovitis"],"prefix":"10.1002","volume":"72","author":[{"given":"Xiaofei","family":"Xu","sequence":"first","affiliation":[{"name":"Erasmus Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Davelaar","sequence":"additional","affiliation":[{"name":"Erasmus Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne\u2010Marie","family":"Mus","sequence":"additional","affiliation":[{"name":"Erasmus Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick S.","family":"Asmawidjaja","sequence":"additional","affiliation":[{"name":"Erasmus Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna M. 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