{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T10:01:23Z","timestamp":1779184883759,"version":"3.51.4"},"reference-count":16,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2013,11,27]],"date-time":"2013-11-27T00:00:00Z","timestamp":1385510400000},"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; Rheumatism"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To determine whether therapeutic strategies that block interleukin\u20106 (IL\u20106) or tumor necrosis factor \u03b1 (TNF\u03b1) can improve the responsiveness of Teff cells to suppression in patients with juvenile idiopathic arthritis (JIA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Synovial fluid mononuclear cells (SFMCs) from the inflamed joints of patients with JIA were cultured in the presence of etanercept or anti\u2013IL\u20106 in vitro, and protein kinase B (PKB)\/c\u2010Akt activation and responsiveness to suppression were measured. In addition, the in vivo effects of TNF\u03b1 blockade were investigated using peripheral blood mononuclear cells obtained from patients before and after the start of etanercept therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In vitro treatment of SFMCs with anti\u2013IL\u20106 led to improved Treg cell\u2013mediated suppression of cell proliferation in some but not all patients. Blocking TNF\u03b1 with etanercept, however, clearly enhanced suppression, especially that of CD8+ T cells. In the presence of etanercept, PKB\/c\u2010Akt activation of Teff cells was reduced, and cells became more susceptible to transforming growth factor \u03b2\u2013mediated suppression, indicating that anti\u2010TNF\u03b1 directly targets resistant Teff cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study is the first to show that anti\u2010TNF\u03b1 targets the resistance of Teff cells to suppression, resulting in improved regulation of inflammatory effector cells.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.38132","type":"journal-article","created":{"date-parts":[[2013,8,27]],"date-time":"2013-08-27T20:48:38Z","timestamp":1377636518000},"page":"3279-3284","source":"Crossref","is-referenced-by-count":30,"title":["Brief Report: Anti\u2013Tumor Necrosis Factor \u03b1 Targets Protein Kinase B\/c\u2010Akt\u2013Induced Resistance of Effector Cells to Suppression in Juvenile Idiopathic Arthritis"],"prefix":"10.1002","volume":"65","author":[{"given":"Ellen J.","family":"Wehrens","sequence":"first","affiliation":[{"name":"Wilhelmina Children's Hospital, University Medical Center Utrecht Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastiaan J.","family":"Vastert","sequence":"additional","affiliation":[{"name":"Wilhelmina Children's Hospital, University Medical Center Utrecht Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerdien","family":"Mijnheer","sequence":"additional","affiliation":[{"name":"Wilhelmina Children's Hospital, University Medical Center Utrecht Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenny","family":"Meerding","sequence":"additional","affiliation":[{"name":"Wilhelmina Children's Hospital, University Medical Center Utrecht Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Klein","sequence":"additional","affiliation":[{"name":"Wilhelmina Children's Hospital, University Medical Center Utrecht Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nico M.","family":"Wulffraat","sequence":"additional","affiliation":[{"name":"Wilhelmina Children's Hospital, University Medical Center Utrecht Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Berent J.","family":"Prakken","sequence":"additional","affiliation":[{"name":"Wilhelmina Children's Hospital, University Medical Center Utrecht Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Femke","family":"van Wijk","sequence":"additional","affiliation":[{"name":"Wilhelmina Children's Hospital, University Medical Center Utrecht Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,11,27]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)60244-4"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2011.04.015"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.2217\/imt.11.147"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20040165"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-11-4567"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.34565"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20061531"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.1.201"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-12-328187"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.30503"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2012.149"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1564"},{"key":"e_1_2_7_14_1","first-page":"1991","article-title":"Revision of the proposed classification criteria for juvenile idiopathic arthritis: Durban, 1997","volume":"25","author":"Petty RE","year":"1998","journal-title":"J Rheumatol"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201041004"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.11.6210"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.259549"}],"container-title":["Arthritis &amp; 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