{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:53:40Z","timestamp":1790787220600,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,2,8]],"date-time":"2025-02-08T00:00:00Z","timestamp":1738972800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,2,8]],"date-time":"2025-02-08T00:00:00Z","timestamp":1738972800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","award":["NIHR2046"],"award-info":[{"award-number":["NIHR2046"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012041","name":"Versus Arthritis","doi-asserted-by":"publisher","award":["19639"],"award-info":[{"award-number":["19639"]}],"id":[{"id":"10.13039\/501100012041","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis & Rheumatology"],"published-print":{"date-parts":[[2025,7]]},"abstract":"\n Objective<\/jats:title>\n \n Genetic associations and blockade of the interleukin (IL)\u201023\/IL\u201017 axis with monoclonal antibodies support a role for this pathway in patients with psoriatic arthritis (PsA). This study examines the requirement of IL\u201023 for IL\u201017 production and the role of the metabolic microenvironment in the expansion of Th\n 17<\/jats:sub>\n \u2010derived cells in patients with PsA.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Th\n 17<\/jats:sub>\n cell frequencies in synovial fluid or peripheral blood from patients with PsA were evaluated by flow cytometry using chemokine receptor 6, CD161, and T\u2010bet as phenotypic markers, and the cytokines interferon \u03b3, granulocyte\u2013macrophage colony\u2010stimulating factor (GM\u2010CSF), and IL\u201017 were assessed by flow cytometry and enzyme\u2010linked immunosorbent assay. The impact of IL\u201023 and metabolic stress on T cell differentiation was investigated.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Polyfunctional positive IL\u201017 (IL\u201017\n pos<\/jats:sup>\n ) CD4 (\n P<\/jats:italic>\n < 0.0001) and CD8 (\n P<\/jats:italic>\n < 0.0001), and GM\u2010CSF\n pos<\/jats:sup>\n Th\n 17<\/jats:sub>\n \u2010derived cells (\n P<\/jats:italic>\n < 0.0001) were increased in the inflamed joints of patients with PsA, with a proportional decrease in the peripheral blood of patients. We demonstrate IL\u201023\u2013independent IL\u201017 release by CD4 T cells in patients with PsA, in which the absence of IL\u201023 during Th\n 17<\/jats:sub>\n differentiation reduced IL\u201017 by mean \u00b1 SEM 31% \u00b1 5.8%. Exogenous IL\u201023 increased IL\u201017, negatively regulated GM\u2010CSF, and cooperated with transforming growth factor \u03b2 to augment IL\u201017. Polyfunctional Th\n 17<\/jats:sub>\n and Th\n 17<\/jats:sub>\n \u2010derived cells, but not Th\n 1<\/jats:sub>\n cells, were expanded by metabolic stress in patients with PsA.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n We confirmed the abundance of polyfunctional type 17 CD4 and CD8 cells in the inflamed joints of patients with PsA. We demonstrate IL\u201023\u2013independent expansion of Th\n 17<\/jats:sub>\n cells, for which IL\u201023 negatively regulates GM\u2010CSF. This may account for therapeutic differences in IL\u201017 and IL\u201023 inhibition in patients with PsA or other spondyloarthritides. Polyfunctional IL\u201017\n pos<\/jats:sup>\n Th\n 17<\/jats:sub>\n and Th\n 17<\/jats:sub>\n \u2010derived but not Th\n 1<\/jats:sub>\n cells were expanded by metabolic stress, and metabolic stress may itself represent a unique therapeutic target.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/art.43095","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T01:46:40Z","timestamp":1734918400000},"page":"842-853","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Metabolic Stress Expands Polyfunctional, Proinflammatory Th\n 17<\/sub>\n Cells in Patients With Psoriatic Arthritis for Whom There is Interleukin\u201023\u2013Independent Interleukin\u201017 Production"],"prefix":"10.1002","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2454-7716","authenticated-orcid":false,"given":"Carmel B.","family":"Stober","sequence":"first","affiliation":[{"name":"University of Cambridge and Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust Cambridge United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Ellis","sequence":"additional","affiliation":[{"name":"University of Cambridge, Cambridge University Hospitals NHS Foundation Trust Cambridge United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane C.","family":"Goodall","sequence":"additional","affiliation":[{"name":"University of Cambridge, Cambridge University Hospitals NHS Foundation Trust Cambridge United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Veldhoen","sequence":"additional","affiliation":[{"name":"GIMM \u2010 Gulbenkian Institute for Molecular Medicine, Avenida Prof. Egas Moniz Lisbon Portugal"},{"name":"Faculdade de Medicina da Universidade de Lisboa Avenida Prof. Egas Moniz Lisbon Portugal"},{"name":"The Babraham Institute Cambridge United\u00a0Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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