{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T00:55:47Z","timestamp":1770512147935,"version":"3.49.0"},"reference-count":22,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2014,6,17]],"date-time":"2014-06-17T00:00:00Z","timestamp":1402963200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Beth Israel Deaconess Medical Center & Harvard Institutes of Medicine"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Immunol Cell Biol"],"published-print":{"date-parts":[[2014,10]]},"abstract":"<jats:p>The regulated control of Ca<jats:sup>2+<\/jats:sup> influx is essential for the activation and function of the adaptive immune response, as Ca<jats:sup>2+<\/jats:sup> is a key regulator of important transcription factors. To determine whether Ca<jats:sup>2+<\/jats:sup> release\u2010activated Ca<jats:sup>2+<\/jats:sup> (CRAC) channels contribute to the abnormal behaviour of T cells in patients with rheumatoid arthritis (RA), we performed a cross\u2010sectional study to characterize the expression and functional status of CRACM1 channels in RA patients. Peripheral blood was obtained from 50 RA patients, 50 osteoarthritis (OA) patients and healthy donors. We measured Ca<jats:sup>2+<\/jats:sup> influx and CRAC currents in na\u00efve and memory CD4<jats:sup>+<\/jats:sup> T cells. CRACM1 expression was evaluated in T cells from each of the three groups. These cells were further characterized by flow cytometric analysis of interleukin\u20104 (IL\u20104), IL\u201017, interferon\u2010\u03b3 and tumour necrosis factor\u2010\u03b1. These cytokines were also measured in na\u00efve CD4<jats:sup>+<\/jats:sup> T cells following the lentivirus\u2010mediated silencing of CRACM1.There was a significant positive correlation between Ca<jats:sup>2+<\/jats:sup> influx in na\u00efve T cells and RA activity. Functionally aberrant na\u00efve CD4<jats:sup>+<\/jats:sup> T cells from patients with active RA showed the different cytokine release pattern and exhibited increased Ca<jats:sup>2+<\/jats:sup> influx as well as increased CRACM1 protein expression and function. Specific lentiviral\u2010induced gene silencing of CRACM1 reversed the alterations in T\u2010cell cytokine production. The data presented here indicate that an upregulation of CRACM1 expression and function may be responsible for the abnormal cytokine release of na\u00efve CD4<jats:sup>+<\/jats:sup> T cells in RA patients. CRACM1 might therefore represent a new molecular target for RA therapies.<\/jats:p>","DOI":"10.1038\/icb.2014.45","type":"journal-article","created":{"date-parts":[[2014,6,17]],"date-time":"2014-06-17T09:41:21Z","timestamp":1402998081000},"page":"752-760","source":"Crossref","is-referenced-by-count":33,"title":["Upregulation of store\u2010operated Ca<sup>2+<\/sup> entry in the na\u00efve CD4<sup>+<\/sup> T cells with aberrant cytokine releasing in active rheumatoid arthritis"],"prefix":"10.1111","volume":"92","author":[{"given":"Shuang","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Ehime University Graduate School of Medicine Ehime Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shohei","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Bone and Joint Surgery, Ehime University Graduate School of Medicine Ehime Japan"},{"name":"Community Health Care Organization Uwajima Hospital Ehime Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masachika","family":"Shudou","sequence":"additional","affiliation":[{"name":"Department of Bioscience, Integrated Center for Sciences, Ehime University Ehime Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miyuki","family":"Kuno","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Physiology, Osaka City University Graduate School of Medicine Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiromasa","family":"Miura","sequence":"additional","affiliation":[{"name":"Department of Bone and Joint Surgery, Ehime University Graduate School of Medicine Ehime Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazutaka","family":"Maeyama","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Ehime University Graduate School of Medicine Ehime Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,6,17]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2412"},{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2005.00245.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2011.05.015"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2006.00370.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0706122105"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(01)00495-7"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-008-0723-4"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00360-08"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1100847"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0605136103"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.56.11.656"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1261"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1001796"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3233"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/13.3.305"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.4161\/chan.5.6.18222"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.1996.tb08288.x"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/35.1.24"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2009.11.001"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.f.220"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2011.05.006"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2009.00822.x"}],"container-title":["Immunology &amp; 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