{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:02:06Z","timestamp":1791219726443,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2015,9,23]],"date-time":"2015-09-23T00:00:00Z","timestamp":1442966400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science, and Technology of Japan (MEXT)","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Japanese Government"},{"name":"MEXT Leading Graduate School Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>We have previously shown that expression of the Bcl\u20103 gene, a member of the I\u03baB family, is down\u2010regulated in CD4+ T cells from patients with rheumatoid arthritis (RA) following tocilizumab therapy. The objective of this study was to examine the role of Bcl\u20103 in the pathogenesis of RA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>DNA microarray analysis was used to compare the signal intensity of Bcl\u20103 in CD4+ T cells from untreated RA patients and healthy controls. We examined the roles of interleukin\u20106 (IL\u20106)\/STAT\u20103 signaling in the induction of Bcl\u20103. In addition, we analyzed the gene expression profiles of Bcl\u20103\u2013transduced CD4+ T cells by RNA sequencing. The effects of enforced expression as well as gene silencing of Bcl\u20103 on the development of follicular helper T (Tfh) cells were evaluated. Finally, we examined correlations between the signal intensities of Bcl\u20103 and Tfh cell\u2013related genes in CD4+ T cells from untreated RA patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Bcl\u20103 levels were significantly higher in RA patients than in healthy controls. IL\u20106 induced Bcl\u20103 expression in CD4+ T cells in a STAT\u20103\u2013dependent manner. Transcriptome analysis revealed that the expression of Bcl\u20106, a master regulator of Tfh cell differentiation, was significantly up\u2010regulated by the enforced Bcl\u20103 expression. The enforced Bcl\u20103 expression increased, but Bcl\u20103 silencing decreased, the numbers of IL\u201021\u2013producing Tfh\u2010like cells. Bcl\u20103 levels in CD4+ T cells from RA patients correlated positively with the levels of Tfh cell\u2013related genes CXCR5, inducible costimulator, and achaete\u2010scute homolog 2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Bcl\u20103 is involved in the development of Tfh cells and the pathogenesis of RA, presumably by inducing IL\u201021 production.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.39266","type":"journal-article","created":{"date-parts":[[2015,7,2]],"date-time":"2015-07-02T10:11:17Z","timestamp":1435831877000},"page":"2651-2660","source":"Crossref","is-referenced-by-count":29,"title":["Role of Bcl\u20103 in the Development of Follicular Helper T Cells and in the Pathogenesis of Rheumatoid Arthritis"],"prefix":"10.1002","volume":"67","author":[{"given":"Kazuyuki","family":"Meguro","sequence":"first","affiliation":[{"name":"Chiba University Graduate School of Medicine Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kotaro","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Chiba University Graduate School of Medicine Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junichi","family":"Hosokawa","sequence":"additional","affiliation":[{"name":"Chiba University Graduate School of Medicine Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshie","family":"Sanayama","sequence":"additional","affiliation":[{"name":"Chiba University Graduate School of Medicine Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeru","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Chiba University Graduate School of Medicine Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunsuke","family":"Furuta","sequence":"additional","affiliation":[{"name":"Chiba University Graduate School of Medicine Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kei","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Chiba University Graduate School of Medicine Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Takatori","sequence":"additional","affiliation":[{"name":"Chiba University Graduate School of Medicine Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Suto","sequence":"additional","affiliation":[{"name":"Chiba University Graduate School of Medicine Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akemi","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"Chiba University Graduate School of Medicine Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Ohara","sequence":"additional","affiliation":[{"name":"Kazusa DNA Research Institute Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Chiba University Graduate School of Medicine Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,9,23]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)60826-4"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1004965"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60784-3"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2009.181"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2416"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0b013e32805e87e0"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0000000000000036"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-031210-101400"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.10.004"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.09.007"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12162"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/827480"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2006.068064"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.23940"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38324"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.01.020"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2012.01102.x"},{"key":"e_1_2_7_19_1","first-page":"1421","article-title":"Prediction of therapeutic responses to tocilizumab in patients with rheumatoid arthritis: biomarkers identified by analysis of gene expression in peripheral blood mononuclear cells using genome\u2010wide DNA microarray. 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