{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T12:48:40Z","timestamp":1790426920308,"version":"4.1.0"},"reference-count":16,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2014,4,28]],"date-time":"2014-04-28T00:00:00Z","timestamp":1398643200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To evaluate the effects of etanercept on the phenotype of CD4+ T helper lymphocytes from patients with juvenile idiopathic arthritis (JIA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We compared the proportions of various Th cell subsets in peripheral blood (PB) from etanercept\u2010treated and untreated JIA patients. An in vitro study was performed on PB mononuclear cells (PBMCs) from 15 children with untreated JIA, in which we evaluated the proliferative response of these cells, as well as their cytokine production profile, in the presence of various stimuli with or without etanercept.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found lower proportions of CD4+ CD161+ (nonclassic) Th1 lymphocytes in the PB of patients treated with etanercept than in untreated patients. In vitro, etanercept inhibited the proliferative response induced by either polyclonal or recall antigen stimulation of PBMCs. Moreover, etanercept increased the proportion of CD4+CD161+ Th17\/Th1 and Th17 cells in vitro while decreasing the proportions of nonclassic Th1 cell subsets, leaving CD4+CD161\u2212 (classic) Th1 cells unaffected. We also found that tumor necrosis factor \u03b1 (TNF\u03b1) was able to induce transition of Th17 lymphocytes toward the nonclassic Th1 phenotype in vitro, probably due to the high expression of TNF receptor type II observed in Th17 cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We have previously demonstrated the occurrence of a shifting of CD4+CD161+ Th17 cells to the nonclassic Th1 phenotype in children with JIA. The present findings suggest that etanercept can exert its disease\u2010modifying action by interfering with this shifting.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.38355","type":"journal-article","created":{"date-parts":[[2014,1,27]],"date-time":"2014-01-27T14:21:37Z","timestamp":1390832497000},"page":"1372-1377","source":"Crossref","is-referenced-by-count":54,"title":["Brief Report: Etanercept Inhibits the Tumor Necrosis Factor \u03b1\u2013Driven Shift of Th17 Lymphocytes Toward a Nonclassic Th1 Phenotype in Juvenile Idiopathic Arthritis"],"prefix":"10.1002","volume":"66","author":[{"given":"Laura","family":"Maggi","sequence":"first","affiliation":[{"name":"University of Florence Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolando","family":"Cimaz","sequence":"additional","affiliation":[{"name":"Anna Meyer Children's Hospital and University of Florence Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Capone","sequence":"additional","affiliation":[{"name":"University of Florence Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Santarlasci","sequence":"additional","affiliation":[{"name":"University of Florence Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Querci","sequence":"additional","affiliation":[{"name":"University of Florence Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Simonini","sequence":"additional","affiliation":[{"name":"Anna Meyer Children's Hospital and University of Florence Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Nencini","sequence":"additional","affiliation":[{"name":"University of Florence Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Liotta","sequence":"additional","affiliation":[{"name":"University of Florence Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Romagnani","sequence":"additional","affiliation":[{"name":"University of Florence Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Maggi","sequence":"additional","affiliation":[{"name":"University of Florence Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Annunziato","sequence":"additional","affiliation":[{"name":"University of Florence Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Cosmi","sequence":"additional","affiliation":[{"name":"University of Florence Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,4,28]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60363-8"},{"key":"e_1_2_6_3_1","first-page":"2116","article-title":"Immunohistological characteristics of T cell infiltrates in different forms of childhood onset chronic arthritis","volume":"23","author":"Murray KJ","year":"1996","journal-title":"J Rheumatol"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2006.061853"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.30331"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20080397"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1003852107"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.30332"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200003163421103"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780400703"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2009.10.012"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.12.013"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200838535"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keq224"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201242648"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1159\/000343467"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2012.05.004"}],"container-title":["Arthritis &amp; 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