{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T15:21:09Z","timestamp":1790781669052,"version":"4.1.0"},"reference-count":15,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,1,28]],"date-time":"2019-01-28T00:00:00Z","timestamp":1548633600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"DOI":"10.13039\/501100000341","name":"Arthritis Research UK","doi-asserted-by":"publisher","award":["award 21141"],"award-info":[{"award-number":["award 21141"]}],"id":[{"id":"10.13039\/501100000341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000341","name":"Arthritis Research UK","doi-asserted-by":"publisher","award":["award 19761"],"award-info":[{"award-number":["award 19761"]}],"id":[{"id":"10.13039\/501100000341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000861","name":"Sparks","doi-asserted-by":"publisher","award":["08ICH09"],"award-info":[{"award-number":["08ICH09"]}],"id":[{"id":"10.13039\/501100000861","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000861","name":"Sparks","doi-asserted-by":"publisher","award":["12ICH08"],"award-info":[{"award-number":["12ICH08"]}],"id":[{"id":"10.13039\/501100000861","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Evidence suggests that aberrant function of innate lymphoid cells (ILCs), whose functional and transcriptional profiles overlap with those of Th cell subsets, contributes to immune\u2010mediated pathologies. To date, analysis of juvenile idiopathic arthritis (JIA) immune pathology has concentrated on the contribution of CD4+ T cells; we have previously identified an expansion of Th17 cells within the synovial fluid (SF) of JIA patients. We undertook this study to extend this analysis to further investigate the role of ILCs and other interleukin\u201017 (IL\u201017)\u2013producing T cell subsets in JIA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>ILCs and CD3+ T cell subsets were defined in peripheral blood mononuclear cells (PBMCs) from healthy adults, healthy children, and JIA patients and in SF mononuclear cells (SFMCs) from JIA patients using flow cytometry. Defined subsets in SFMCs were correlated with clinical measures including physician's global assessment of disease activity on a visual analog scale, number of joints with active disease, and erythrocyte sedimentation rate. Transcription factor and cytokine profiles of sorted ILCs were assessed by quantitative reverse transcriptase\u2013polymerase chain reaction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Group 1 ILCs (ILC1s), NKp44\u2212 group 3 ILCs (natural cytotoxicity receptor\u2013negative [NCR\u2212] ILC3s), and NKp44+ ILC3s (NCR+ ILC3s) were enriched in JIA SFMCs compared to PBMCs, which corresponded to an increase in transcripts for <jats:italic>TBX21<\/jats:italic>,<jats:italic> IFNG<\/jats:italic>, and <jats:italic>IL17A<\/jats:italic>. Of the ILC subsets, the frequency of NCR\u2212 ILC3s in JIA SFMCs displayed the strongest positive association with clinical measures, which was mirrored by an expansion in IL\u201017A+CD4+, IL\u201017A+CD8+, and IL\u201017A+ \u03b3\u03b4 T cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We demonstrate that the strength of the IL\u201017A signature in JIA SFMCs is determined by multiple lymphoid cell types, including NCR\u2212 ILC3s and IL\u201017A+CD4+, IL\u201017A+CD8+, and IL\u201017A+ \u03b3\u03b4 T cells. These observations may have important implications for the development of stratified therapeutics.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.40731","type":"journal-article","created":{"date-parts":[[2018,10,23]],"date-time":"2018-10-23T02:14:13Z","timestamp":1540260853000},"page":"460-467","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Innate Lymphoid Cells and T Cells Contribute to the Interleukin\u201017A Signature Detected in the Synovial Fluid of Patients With Juvenile Idiopathic Arthritis"],"prefix":"10.1002","volume":"71","author":[{"given":"Elizabeth C.","family":"Rosser","sequence":"first","affiliation":[{"name":"University College London Great Ormond Street Institute of Child Health and Arthritis Research UK Centre for Adolescent Rheumatology at University College London University College London Hospitals, and Great Ormond Street Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Lom","sequence":"additional","affiliation":[{"name":"University College London Great Ormond Street Institute of Child Health and Arthritis Research UK Centre for Adolescent Rheumatology at University College London University College London Hospitals, and Great Ormond Street Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0071-1163","authenticated-orcid":false,"given":"David","family":"Bending","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Immunotherapy College of Medical and Dental Sciences University of Birmingham  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4063-8549","authenticated-orcid":false,"given":"Chantal L.","family":"Duurland","sequence":"additional","affiliation":[{"name":"University College London Great Ormond Street Institute of Child Health  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona","family":"Bajaj\u2010Elliott","sequence":"additional","affiliation":[{"name":"University College London Great Ormond Street Institute of Child Health  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7495-1429","authenticated-orcid":false,"given":"Lucy R.","family":"Wedderburn","sequence":"additional","affiliation":[{"name":"University College London Great Ormond Street Institute of Child Health, Arthritis Research UK Centre for Adolescent Rheumatology at University College London, University College London Hospitals, and Great Ormond Street Hospital, and NIHR Biomedical Research Centre at Great Ormond Street Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,1,28]]},"reference":[{"key":"e_1_2_7_2_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_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.23291"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14189"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-11-427781"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.1997.4331330.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4373"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.34355"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39261"},{"key":"e_1_2_7_10_1","first-page":"515","article-title":"Interleukin 17 levels are increased in juvenile idiopathic arthritis synovial fluid and induce synovial fibroblasts to produce proinflammatory cytokines and matrix metalloproteinases","volume":"35","author":"Agarwal S","year":"2008","journal-title":"J Rheumatol"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2012.00124"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.11.6173"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2006.061853"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2416"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3368"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1505066"}],"container-title":["Arthritis &amp; 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