{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:08:03Z","timestamp":1790766483288,"version":"4.1.0"},"reference-count":19,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2014,6,27]],"date-time":"2014-06-27T00:00:00Z","timestamp":1403827200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["097259"],"award-info":[{"award-number":["097259"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2014,7]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Granulocyte\u2013macrophage colony stimulating factor (GM\u2010CSF) is a potent inflammatory mediator that is responsible for recruitment and activation of innate immune cells. Recent data from murine studies have identified Th17 cells as a key source of GM\u2010CSF and suggest that T cell\u2013derived GM\u2010CSF is instrumental in the induction of autoimmune disease. The present study was undertaken to analyze the expression of T cell\u2013derived GM\u2010CSF in the joints of patients with juvenile idiopathic arthritis (JIA) and to investigate the differentiation of Th17 cells and how this relates to GM\u2010CSF+ T helper cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Synovial fluid (SF) and peripheral blood (PB) samples from 24 patients with JIA were analyzed, by flow cytometry and reverse transcription\u2013polymerase chain reaction, for expression of GM\u2010CSF and the Th17 marker CD161. A cytokine capture assay was used to purify Th17 cells and test the plasticity of cytokine production in response to interleukin\u201012 (IL\u201012) and IL\u201023.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The frequency of GM\u2010CSF\u2013producing T helper cells was significantly enriched in SF mononuclear cells compared to PB mononuclear cells from the patients with JIA (24.1% of CD4+ T cells versus 2.9%) and closely correlated with the erythrocyte sedimentation rate (r<jats:sup>2<\/jats:sup> = 0.91, <jats:italic>P<\/jats:italic> &lt; 0.001). Synovial GM\u2010CSF+ T cells were predominantly CD161+ and coexpressed interferon\u2010\u03b3 (IFN\u03b3), but not IL\u201017. Culture of Th17 cells in the presence of IL\u201012 led to rapid up\u2010regulation of GM\u2010CSF and IFN\u03b3, recapitulating the phenotype of GM\u2010CSF\u2013expressing cells within the joint.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results identify a novel outcome of Th17 plasticity in humans that may account for the enrichment of GM\u2010CSF\u2013expressing T cells in the joints of patients with JIA. The association of GM\u2010CSF expression with systemic inflammation highlights the potential role of Th17\u2010related cytokines in the pathology of JIA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.38647","type":"journal-article","created":{"date-parts":[[2014,4,1]],"date-time":"2014-04-01T14:09:47Z","timestamp":1396361387000},"page":"1955-1960","source":"Crossref","is-referenced-by-count":64,"title":["Brief Report: T Cell Expression of Granulocyte\u2013Macrophage Colony\u2010Stimulating Factor in Juvenile Arthritis Is Contingent Upon Th17 Plasticity"],"prefix":"10.1002","volume":"66","author":[{"given":"Christopher","family":"Piper","sequence":"first","affiliation":[{"name":"University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne M.","family":"Pesenacker","sequence":"additional","affiliation":[{"name":"University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Bending","sequence":"additional","affiliation":[{"name":"University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balathas","family":"Thirugnanabalan","sequence":"additional","affiliation":[{"name":"University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hemlata","family":"Varsani","sequence":"additional","affiliation":[{"name":"University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy R.","family":"Wedderburn","sequence":"additional","affiliation":[{"name":"University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiran","family":"Nistala","sequence":"additional","affiliation":[{"name":"University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,6,27]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-1-4160-3285-4.10097-X"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.10710"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20030896"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.23291"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.30332"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2027"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2031"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.1997.4331330.x"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2009.178"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.30354"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1002923"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-04-216085"},{"key":"e_1_2_7_14_1","first-page":"390","article-title":"International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001","volume":"31","author":"Petty RE","year":"2004","journal-title":"J Rheumatol"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1003852107"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20080397"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1993"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20070663"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/anr.1780320805"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-202450"}],"container-title":["Arthritis &amp; Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.38647","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.38647","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T14:44:44Z","timestamp":1759934684000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/art.38647"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,6,27]]},"references-count":19,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2014,7]]}},"alternative-id":["10.1002\/art.38647"],"URL":"https:\/\/doi.org\/10.1002\/art.38647","archive":["Portico"],"relation":{},"ISSN":["2326-5191","2326-5205"],"issn-type":[{"value":"2326-5191","type":"print"},{"value":"2326-5205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,6,27]]}}}