{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T01:54:29Z","timestamp":1791338069511,"version":"4.3.1"},"reference-count":116,"publisher":"Wiley","license":[{"start":{"date-parts":[[2016,1,1]],"date-time":"2016-01-01T00:00:00Z","timestamp":1451606400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["KAKENHI 15K19472"],"award-info":[{"award-number":["KAKENHI 15K19472"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["CSFPAJT-88887.091277\/2014-00"],"award-info":[{"award-number":["CSFPAJT-88887.091277\/2014-00"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["KAKENHI 15K19472"],"award-info":[{"award-number":["KAKENHI 15K19472"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["CSFPAJT-88887.091277\/2014-00"],"award-info":[{"award-number":["CSFPAJT-88887.091277\/2014-00"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Mediators of Inflammation"],"published-print":{"date-parts":[[2016]]},"abstract":"<jats:p>Several animal and human studies have implicated CD4+ T helper 17 (Th17) cells and their downstream pathways in the pathogenesis of central nervous system (CNS) autoimmunity in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD), challenging the traditional Th1-Th2 paradigm. Th17 cells can efficiently cross the blood-brain barrier using alternate ways from Th1 cells, promote its disruption, and induce the activation of other inflammatory cells in the CNS. A number of environmental factors modulate the activity of Th17 pathways, so changes in the diet, exposure to infections, and other environmental factors can potentially change the risk of development of autoimmunity. Currently, new drugs targeting specific points of the Th17 pathways are already being tested in clinical trials and provide basis for the development of biomarkers to monitor disease activity. Herein, we review the key findings supporting the relevance of the Th17 pathways in the pathogenesis of MS and NMOSD, as well as their potential role as therapeutic targets in the treatment of immune-mediated CNS disorders.<\/jats:p>","DOI":"10.1155\/2016\/5314541","type":"journal-article","created":{"date-parts":[[2016,1,28]],"date-time":"2016-01-28T21:27:40Z","timestamp":1454016460000},"page":"1-11","source":"Crossref","is-referenced-by-count":66,"title":["Th17 Cells Pathways in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders: Pathophysiological and Therapeutic Implications"],"prefix":"10.1155","volume":"2016","author":[{"given":"Giordani Rodrigues Dos","family":"Passos","sequence":"first","affiliation":[{"name":"Brain Institute and Department of Neurology, Faculty of Medicine, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Avenida Ipiranga 6690, 90610-000 Porto Alegre, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas Kazutoshi","family":"Sato","sequence":"additional","affiliation":[{"name":"Brain Institute and Department of Neurology, Faculty of Medicine, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Avenida Ipiranga 6690, 90610-000 Porto Alegre, RS, Brazil"},{"name":"Department of Neurology and LIM-15, Faculty of Medicine, University of Sao Paulo (USP), Avenida Dr. Arnaldo 455, 01246-903 S\u00e3o Paulo, SP, Brazil"},{"name":"Department of Multiple Sclerosis Therapeutics, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aobaku, Sendai, Miyagi 980-8574, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jefferson","family":"Becker","sequence":"additional","affiliation":[{"name":"Brain Institute and Department of Neurology, Faculty of Medicine, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Avenida Ipiranga 6690, 90610-000 Porto Alegre, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuo","family":"Fujihara","sequence":"additional","affiliation":[{"name":"Department of Multiple Sclerosis Therapeutics, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aobaku, Sendai, Miyagi 980-8574, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(08)61620-7"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1759-1961.2012.00030.x"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.0000000000001729"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0098192"},{"issue":"7","key":"5","doi-asserted-by":"crossref","first-page":"2348","DOI":"10.4049\/jimmunol.136.7.2348","volume":"136","year":"1986","journal-title":"The Journal of Immunology"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2013.03.002"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2014.03.009"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.1038\/ni1254"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.1038\/ni1261"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20041257"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.1038\/nature01355"},{"key":"12","doi-asserted-by":"publisher","DOI":"10.1038\/nature09447"},{"key":"13","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2014.07.013"},{"key":"14","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1993"},{"key":"15","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21748"},{"key":"16","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2031"},{"key":"17","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20071119"},{"key":"18","doi-asserted-by":"publisher","DOI":"10.1084\/jem.194.7.873"},{"key":"19","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2027"},{"key":"20","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2014.154"},{"key":"21","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.1.566"},{"key":"22","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20071978"},{"key":"23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0015531"},{"key":"24","doi-asserted-by":"publisher","DOI":"10.1038\/nature11337"},{"key":"25","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2013.09.009"},{"key":"26","doi-asserted-by":"publisher","DOI":"10.1038\/nature06880"},{"key":"27","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.09.033"},{"key":"28","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.08.020"},{"key":"29","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2013.06.016"},{"key":"30","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12029"},{"key":"31","doi-asserted-by":"publisher","DOI":"10.4172\/2155-9562.S12-004"},{"key":"32","doi-asserted-by":"publisher","DOI":"10.1038\/nature11868"},{"key":"33","doi-asserted-by":"publisher","DOI":"10.1038\/nature11984"},{"key":"34","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2014-307928"},{"key":"35","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-010-9466-6"},{"key":"36","doi-asserted-by":"publisher","DOI":"10.1038\/nm1651"},{"key":"37","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20072404"},{"key":"38","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1716"},{"key":"39","doi-asserted-by":"publisher","DOI":"10.1096\/fj.09-141978"},{"key":"40","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20110434"},{"key":"41","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20140540"},{"key":"42","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2010.01.014"},{"key":"43","doi-asserted-by":"publisher","DOI":"10.1177\/135245859900500206"},{"key":"44","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awp289"},{"key":"45","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21652"},{"issue":"4","key":"46","first-page":"202","volume":"7","year":"2010","journal-title":"Iranian Journal of Immunology"},{"key":"47","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2015.01.001"},{"key":"48","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2008.070690"},{"key":"49","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0057820"},{"key":"50","doi-asserted-by":"publisher","DOI":"10.1159\/000116923"},{"key":"51","doi-asserted-by":"publisher","DOI":"10.3109\/08923979809034820"},{"key":"52","doi-asserted-by":"publisher","DOI":"10.1177\/1352458510379247"},{"key":"53","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2008.02837.x"},{"key":"54","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2011.03.009"},{"key":"55","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0015050"},{"key":"56","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxr056"},{"key":"57","doi-asserted-by":"publisher","DOI":"10.3390\/ijms131012970"},{"key":"58","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.12118"},{"key":"59","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23651"},{"key":"60","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh453"},{"key":"61","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000326589.57128.c3"},{"key":"62","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2012.12.022"},{"key":"63","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-012-9780-2"},{"key":"64","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12733"},{"key":"65","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-011-0824-0"},{"key":"66","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12098"},{"key":"67","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-015-0207-1"},{"key":"68","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2012.0040"},{"key":"69","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2011.01.031"},{"key":"70","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0061835"},{"key":"71","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0404.2009.01158.x"},{"key":"72","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2014.08.623"},{"key":"73","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2010.12.1102"},{"key":"74","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-012-9752-6"},{"key":"75","doi-asserted-by":"publisher","DOI":"10.1172\/jci33342"},{"key":"76","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2011.03.007"},{"key":"77","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0803227"},{"key":"78","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2110"},{"key":"79","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-011-8296-5"},{"key":"80","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.0b013e318259e123"},{"key":"81","doi-asserted-by":"publisher","DOI":"10.1159\/000227277"},{"key":"82","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.0b013e3181f8832e"},{"key":"83","doi-asserted-by":"publisher","DOI":"10.1177\/1352458512439439"},{"key":"84","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2010.04.022"},{"key":"85","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-003-0979-2"},{"key":"86","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2007.01807.x"},{"key":"87","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2011.02.027"},{"key":"88","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181ebdd64"},{"key":"89","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2014.01.008"},{"key":"90","doi-asserted-by":"publisher","DOI":"10.1177\/1352458511431973"},{"key":"91","doi-asserted-by":"publisher","DOI":"10.5692\/clinicalneurol.53.513"},{"key":"92","doi-asserted-by":"publisher","DOI":"10.1172\/jci67554"},{"key":"93","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.100119"},{"key":"94","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa044397"},{"key":"95","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2011.216"},{"key":"96","doi-asserted-by":"publisher","DOI":"10.1177\/1352458511421185"},{"key":"97","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2014.01.035"},{"key":"98","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.m112.383380"},{"key":"99","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23784"},{"key":"100","doi-asserted-by":"publisher","DOI":"10.1097\/nrl.0b013e3181b126e3"},{"key":"101","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2015.02.007"},{"key":"102","doi-asserted-by":"publisher","DOI":"10.1177\/1352458514541978"},{"key":"103","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2011.38"},{"key":"104","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2014.141"},{"key":"105","doi-asserted-by":"publisher","DOI":"10.1016\/j.nrl.2013.12.022"},{"key":"106","doi-asserted-by":"publisher","DOI":"10.1002\/art.30314"},{"key":"107","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keu004"},{"key":"108","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-013-2352-x"},{"key":"109","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-011-1867-1"},{"key":"110","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-014-3030-2"},{"key":"111","doi-asserted-by":"publisher","DOI":"10.1016\/s1474-4422(08)70173-x"},{"key":"112","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22637"},{"key":"113","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-202371"},{"key":"114","doi-asserted-by":"publisher","DOI":"10.1177\/1352458512461105"},{"key":"115","doi-asserted-by":"publisher","DOI":"10.1586\/ern.13.17"},{"key":"116","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2008.08.030"}],"container-title":["Mediators of Inflammation"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/mi\/2016\/5314541.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/mi\/2016\/5314541.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/mi\/2016\/5314541.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T01:14:26Z","timestamp":1718327666000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.hindawi.com\/journals\/mi\/2016\/5314541\/"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016]]},"references-count":116,"alternative-id":["5314541","5314541"],"URL":"https:\/\/doi.org\/10.1155\/2016\/5314541","relation":{},"ISSN":["0962-9351","1466-1861"],"issn-type":[{"value":"0962-9351","type":"print"},{"value":"1466-1861","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016]]}}}