{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T13:41:00Z","timestamp":1793367660838,"version":"4.5.0"},"reference-count":28,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2012,5,25]],"date-time":"2012-05-25T00:00:00Z","timestamp":1337904000000},"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":[[2012,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Tofacitinib (CP\u2010690,550) is a novel JAK inhibitor that is currently in clinical trials for the treatment of rheumatoid arthritis (RA). The aim of this study was to examine the effects of tofacitinib in vitro and in vivo in RA, in order to elucidate the role of JAK in the disease process.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>CD4+ T cells, CD14+ monocytes, and synovial fibroblasts (SFs) were purified from the synovium and peripheral blood of patients with RA and were evaluated for the effect of tofacitinib on cytokine production and cell proliferation. For in vivo analysis, synovium and cartilage samples obtained from patients with RA were implanted in immunodeficient mice (SCID\u2010HuRAg mice), and tofacitinib was administered via an osmotic minipump.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Tofacitinib treatment of CD4+ T cells originating from synovium and peripheral blood inhibited the production of interleukin\u201017 (IL\u201017) and interferon\u2010\u03b3 (IFN\u03b3) in a dose\u2010dependent manner, affecting both proliferation and transcription, but had no effect on IL\u20106 and IL\u20108 production. Tofacitinib did not affect IL\u20106 and IL\u20108 production by RASFs and CD14+ monocytes. However, conditioned medium from CD4+ T cells cultured with tofacitinib inhibited IL\u20106 production by RASFs and IL\u20108 production by CD14+ monocytes. Treatment of SCID\u2010HuRAg mice with tofacitinib decreased serum levels of human IL\u20106 and IL\u20108 and markedly suppressed invasion of synovial tissue into cartilage.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Tofacitinib directly suppressed the production of IL\u201017 and IFN\u03b3 and the proliferation of CD4+ T cells, resulting in inhibition of IL\u20106 production by RASFs and IL\u20108 production by CD14+ cells and decreased cartilage destruction. In CD4+ T cells, presumably Th1 and Th17 cells, JAK plays a crucial role in RA synovitis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.34329","type":"journal-article","created":{"date-parts":[[2011,12,6]],"date-time":"2011-12-06T21:17:56Z","timestamp":1323206276000},"page":"1790-1798","source":"Crossref","is-referenced-by-count":212,"title":["The JAK inhibitor tofacitinib regulates synovitis through inhibition of interferon\u2010\u03b3 and interleukin\u201017 production by human CD4+ T cells"],"prefix":"10.1002","volume":"64","author":[{"given":"Keisuke","family":"Maeshima","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunihiro","family":"Yamaoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Kubo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhisa","family":"Nakano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeru","family":"Iwata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuyoshi","family":"Saito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanobu","family":"Ohishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisaaki","family":"Miyahara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Ishii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hironobu","family":"Yoshimatsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiya","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,5,25]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2008.09.010"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2009.82"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.270.5237.797"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/377065a0"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar2365"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.24567"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2009.108159"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/acr.20494"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1087061"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1358"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1186\/1476-9255-7-41"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1003668"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-02-0769"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780310302"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2050"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kep099"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.10623"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.20303"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e3181f24e59"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20061198"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.tp.0000177643.05739.cd"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa032534"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21778"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.22025"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e31818bbea7"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2007.00506.x"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2007.00504.x"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903566"}],"container-title":["Arthritis &amp; 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