{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:33:59Z","timestamp":1791326039997,"version":"4.3.1"},"reference-count":15,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2017,8,8]],"date-time":"2017-08-08T00:00:00Z","timestamp":1502150400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100006662","name":"National Institute on Handicapped Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006662","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Group 3 innate lymphoid cells (ILC3s) play a pivotal role in barrier tissues such as the gut and the skin, two important sites of disease in spondyloarthritis (SpA). This study was undertaken to investigate whether normal or injured human enthesis, a key target tissue in early SpA, harbors ILC3s in entheseal soft tissue and adjacent perientheseal bone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Interspinous ligament and spinous process bone from donors with no systemic inflammatory disease were collected, enzymatically digested, and immunophenotyped. The immunologic profile of entheseal cells was examined, and the transcriptional profile of sorted ILC3s was compared to that of ILC3s isolated from SpA synovial fluid (SF). To assess the ability of entheseal tissue to produce interleukin\u201017 (IL\u201017) and IL\u201022, entheseal digests were stimulated with IL\u201023 and IL\u20101\u03b2. Osteoarthritic and ruptured Achilles tendon tissue was examined histologically.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The proportion of ILCs in human entheseal soft tissue was higher than that in peripheral blood (<jats:italic>P<\/jats:italic>\u2009=\u20090.008); entheseal soft tissue and perientheseal bone both had a higher proportion of NKp44+ ILC3s (<jats:italic>P<\/jats:italic>\u2009=\u20090.001 and <jats:italic>P<\/jats:italic>\u2009=\u20090.043, respectively). Studies of retinoic acid receptor\u2013related orphan nuclear receptor \u03b3t (ROR\u03b3t), STAT3, and IL\u201023 receptor transcript expression validated the entheseal ILC3 phenotype. Cytokine transcript expression was similar in ILC3s isolated from enthesis and from SpA SF. Stimulation of normal entheseal digests with IL\u201023\/IL\u20101\u03b2 led to up\u2010regulation of IL\u201017A transcript, and histologic examination of injured\/damaged entheses revealed the presence of ROR\u03b3t\u2010expressing cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This work shows that human enthesis harbors a resident population of ILC3s, with the potential to participate in the pathogenesis of SpA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.40150","type":"journal-article","created":{"date-parts":[[2017,5,16]],"date-time":"2017-05-16T17:56:44Z","timestamp":1494957404000},"page":"1816-1822","source":"Crossref","is-referenced-by-count":150,"title":["Brief Report: Group 3 Innate Lymphoid Cells in Human Enthesis"],"prefix":"10.1002","volume":"69","author":[{"given":"Richard J.","family":"Cuthbert","sequence":"first","affiliation":[{"name":"University of Leeds Leeds UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evangelos M.","family":"Fragkakis","sequence":"additional","affiliation":[{"name":"University of Leeds and The Leeds Teaching Hospitals NHS Trust Leeds UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Dunsmuir","sequence":"additional","affiliation":[{"name":"The Leeds Teaching Hospitals NHS Trust Leeds UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Li","sequence":"additional","affiliation":[{"name":"University of York York UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Coles","sequence":"additional","affiliation":[{"name":"University of York York UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Marzo\u2010Ortega","sequence":"additional","affiliation":[{"name":"University of Leeds and NIHR\u2010Leeds Musculoskeletal and Biomedical Research Unit, Leeds Teaching Hospital Trust Leeds UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter V.","family":"Giannoudis","sequence":"additional","affiliation":[{"name":"University of Leeds Leeds UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Jones","sequence":"additional","affiliation":[{"name":"University of Leeds Leeds UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasser M.","family":"El\u2010Sherbiny","sequence":"additional","affiliation":[{"name":"University of Leeds and NIHR\u2010Leeds Musculoskeletal and Biomedical Research Unit, Leeds Teaching Hospital Trust, Leeds, UK, and Mansoura University Hospitals, Mansoura University Mansoura Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"McGonagle","sequence":"additional","affiliation":[{"name":"University of Leeds and NIHR\u2010Leeds Musculoskeletal and Biomedical Research Unit, Leeds Teaching Hospital Trust Leeds UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,8,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2817"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(97)12004-9"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20070906"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1962"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3365"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-051914-021944"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2014-206323"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39261"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2013.477"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-201545"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0117855"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-012-9774-0"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2016-eular.3047"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39732"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2534"}],"container-title":["Arthritis &amp; 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