{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T13:36:34Z","timestamp":1789565794901,"version":"build-2803163510"},"reference-count":108,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,11,1]],"date-time":"2018-11-01T00:00:00Z","timestamp":1541030400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000411","name":"Raynaud's and Scleroderma Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Clin Investigation"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Th17 cells have nonredundant roles in maintaining immunity, particularly at mucosal surfaces. These roles are achieved principally through the production of cytokines and the recruitment of other immune cells to maintain the integrity of mucosal barriers and prevent the dissemination of microorganisms. Th17 cells are heterogeneous and exhibit a considerable degree of plasticity. This allows these cells to respond to changing environmental challenges. However, Th17 cells also play pro\u2010inflammatory roles in chronic autoimmune diseases. The trigger(s) that initiate these Th17 responses in chronic autoimmune diseases remain unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>In this report, we provide an overview of studies involving animal models, patient data, genome wide association studies and clinical trials targeting <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201017 for treatment of patients to gain a better understanding of the pathogenic roles of Th17 cells play in a range of autoimmune diseases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The report sheds light on likely triggers that initiate or perpetuate Th17 responses that promote chronic inflammation and autoimmunity. The divergent effects of tumour necrosis factor alpha blockade on Th17 cells in patients, is explored. Furthermore, we highlight the role of Th17 cells in inducing autoreactive B cells, leading to autoantibody production. Pathogenic bacterial species can change Th17 cell phenotype and responses. These findings provide insights into how Th17 cells could be induced to promoting autoimmune disease pathogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This article provides an overview of the distinct roles Th17 cells play in maintaining immunity at mucosal surfaces and in skin mucosa and how their functional flexibility could be linked with chronic inflammation in autoimmune rheumatic diseases.<\/jats:p><\/jats:sec>","DOI":"10.1111\/eci.13032","type":"journal-article","created":{"date-parts":[[2018,10,6]],"date-time":"2018-10-06T09:55:32Z","timestamp":1538819732000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Functional and phenotypic heterogeneity of Th17 cells in health and disease"],"prefix":"10.1111","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6458-3028","authenticated-orcid":false,"given":"Jonas","family":"Bystrom","sequence":"first","affiliation":[{"name":"William Harvey Research Institute Queen Mary University of London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix I. L.","family":"Clanchy","sequence":"additional","affiliation":[{"name":"Kennedy Institute of Rheumatology University of Oxford Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taher E.","family":"Taher","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Immunotherapy University of Birmingham Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Al\u2010Bogami","sequence":"additional","affiliation":[{"name":"Radiology Department Alnakheel Medical Centre Riyadh Kingdom of Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Voon H.","family":"Ong","sequence":"additional","affiliation":[{"name":"Centre for Rheumatology and Connective Tissue Diseases University College London Royal Free Hospital London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Abraham","sequence":"additional","affiliation":[{"name":"Centre for Rheumatology and Connective Tissue Diseases University College London Royal Free Hospital London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard O.","family":"Williams","sequence":"additional","affiliation":[{"name":"Kennedy Institute of Rheumatology University of Oxford Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rizgar A.","family":"Mageed","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute Queen Mary University of London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,11]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.50"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3512"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.06.001"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2011-201024"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27203"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0802948"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.07.007"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1225152"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20111703"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2007.02687.x"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1720"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature16460"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/v5030777"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1200439"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.9.6536"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.12.002"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-05-1461"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-002-1101-8"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.06.001"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1502641"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2552"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.08.058"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.09.016"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-007-8014-9"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201747102"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.11.009"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201545713"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.11.009"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10957"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.01.002"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1993"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1651"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4199"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.02.009"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3432"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep24072"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0022-202x.2001.01494.x"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2412"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1817"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.34565"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.40180"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-03-272153"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11868"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0023629"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1552"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3579"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1004965"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27186"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar1733"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar4179"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.30093"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20061775"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20062259"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.34477"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar3431"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-016-3480-9"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38617"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201646477"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0806044105"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar3546"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar4416"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)61128-3"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1302313"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2133.2002.04743.x"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20031482"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1001001"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2012.10899.x"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1314258"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12468941"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6621"},{"key":"e_1_2_11_72_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903520"},{"key":"e_1_2_11_73_1","first-page":"3188","article-title":"Interleukin\u201021 is associated with the severity of psoriasis vulgaris through promoting CD4\u00a0+\u00a0 T cells to differentiate into Th17 cells","volume":"8","author":"Wang Y","year":"2016","journal-title":"Am J Transl Res"},{"issue":"923","key":"e_1_2_11_74_1","first-page":"e928","article-title":"beta\u2010Defensin 2 is a responsive biomarker of IL\u201017A\u2010driven skin pathology in patients with psoriasis","volume":"139","author":"Kolbinger F","year":"2017","journal-title":"J Allergy Clin Immunol"},{"key":"e_1_2_11_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)60128-8"},{"key":"e_1_2_11_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.468"},{"key":"e_1_2_11_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2012.05.015"},{"key":"e_1_2_11_78_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-02890-0"},{"key":"e_1_2_11_79_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.12.8761"},{"key":"e_1_2_11_80_1","doi-asserted-by":"publisher","DOI":"10.1177\/0961203318762598"},{"key":"e_1_2_11_81_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kew508"},{"key":"e_1_2_11_82_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kep270"},{"key":"e_1_2_11_83_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0902232"},{"key":"e_1_2_11_84_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0900385"},{"key":"e_1_2_11_85_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1741"},{"key":"e_1_2_11_86_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0806188"},{"key":"e_1_2_11_87_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0000000000000214"},{"key":"e_1_2_11_88_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.1711660307"},{"key":"e_1_2_11_89_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200011)43:11<2455::AID-ANR12>3.0.CO;2-K"},{"key":"e_1_2_11_90_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.40390"},{"key":"e_1_2_11_91_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar4334"},{"key":"e_1_2_11_92_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-016-0993-2"},{"key":"e_1_2_11_93_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00055"},{"key":"e_1_2_11_94_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.30320"},{"key":"e_1_2_11_95_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2467"},{"key":"e_1_2_11_96_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.090421"},{"key":"e_1_2_11_97_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.689"},{"key":"e_1_2_11_98_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2007.27"},{"key":"e_1_2_11_99_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.200"},{"key":"e_1_2_11_100_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-201888"},{"key":"e_1_2_11_101_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2016-210645"},{"key":"e_1_2_11_102_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7916"},{"key":"e_1_2_11_103_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.583"},{"key":"e_1_2_11_104_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38136"},{"key":"e_1_2_11_105_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.01202"},{"key":"e_1_2_11_106_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1109997"},{"key":"e_1_2_11_107_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1503824"},{"key":"e_1_2_11_108_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.14451"},{"key":"e_1_2_11_109_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2004.05.001"}],"container-title":["European Journal of Clinical Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Feci.13032","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/eci.13032","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T20:30:04Z","timestamp":1694809804000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/eci.13032"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11]]},"references-count":108,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,1]]}},"alternative-id":["10.1111\/eci.13032"],"URL":"https:\/\/doi.org\/10.1111\/eci.13032","archive":["Portico"],"relation":{},"ISSN":["0014-2972","1365-2362"],"issn-type":[{"value":"0014-2972","type":"print"},{"value":"1365-2362","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11]]},"assertion":[{"value":"2018-02-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-11-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13032"}}