{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T18:34:23Z","timestamp":1768674863326,"version":"3.49.0"},"reference-count":44,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2014,8,21]],"date-time":"2014-08-21T00:00:00Z","timestamp":1408579200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001700","name":"The Ministry of Education, Culture, Sports, Science and Technology of Japan","doi-asserted-by":"crossref","award":["24591471"],"award-info":[{"award-number":["24591471"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2014,9]]},"abstract":"Summary<\/jats:title>Background<\/jats:title>Regulatory T cells (Tregs<\/jats:sub>) are activated during anergy in response to T cell receptor (TCR<\/jats:styled-content>) activation and functional immune suppression. Anergy of paediatric Tregs<\/jats:sub> is partially dependent on intracellular calcium mobility; following TCR<\/jats:styled-content> activation, Tregs<\/jats:sub> do not exhibit increased intracellular Ca2+<\/jats:sup> concentration ([Ca2+<\/jats:sup>]i<\/jats:sub>).<\/jats:p><\/jats:sec>Objective<\/jats:title>We determined whether [Ca2+<\/jats:sup>]i<\/jats:sub> in adult Tregs<\/jats:sub> defined their anergy, if intracellular Ca2+<\/jats:sup> movement was linked to regulatory functions, whether [Ca2+<\/jats:sup>]i<\/jats:sub> was indicative of asthma pathology, and the potential molecular mechanism responsible for Ca2+<\/jats:sup> movement in Tregs<\/jats:sub>.<\/jats:p><\/jats:sec>Methods<\/jats:title>Tregs<\/jats:sub> were purified by the magnetic bead method, and their regulatory functions were assessed by monitoring carboxyfluorescein succinimidyl ester\u2010labelled responder T cell proliferation. The Ca2+<\/jats:sup> response of Fura\u20102\u2010labelled cells was measured using a video image analysis system. To analyse the functions of Tregs<\/jats:sub> at the molecular level, we generated Jurkat Tet\u2010On\u00ae<\/jats:sup> clones with doxycycline (Dox)\u2010induced forkhead box P3 (FOXP<\/jats:styled-content>3) protein expression.<\/jats:p><\/jats:sec>Results<\/jats:title>CD<\/jats:styled-content>4+<\/jats:sup>CD<\/jats:styled-content>25+<\/jats:sup>CD<\/jats:styled-content>127\u2212\/low<\/jats:sup> Tregs<\/jats:sub> from participants without asthma did not elicit Ca2+<\/jats:sup> influx in response to TCR<\/jats:styled-content> activation, exhibited little proliferation and suppressed proliferation of CD<\/jats:styled-content>4+<\/jats:sup>CD<\/jats:styled-content>25\u2212<\/jats:sup> T cells. In contrast, under similar conditions, Tregs<\/jats:sub> from patients with asthma exhibited increased [Ca2+<\/jats:sup>]i<\/jats:sub> and robust proliferation with partial loss of regulatory functions. FOXP<\/jats:styled-content>3 protein levels in Tet\u2010On\u00ae<\/jats:sup> clones were high after both 2\u2010 and 5\u2010day Dox treatment; however, 5\u2010day cells were comparable with Tregs<\/jats:sub> from patients with asthma, whereas 2\u2010day cells were similar to Tregs<\/jats:sub> from participants without asthma. Increasing [Ca2+<\/jats:sup>]i<\/jats:sub> induced a high level of receptor for activated C kinase 1 (RACK<\/jats:styled-content>1) expression in 5\u2010day cells.<\/jats:p><\/jats:sec>Conclusions and Clinical Relevance<\/jats:title>We confirmed that Tregs<\/jats:sub> in patients with asthma are functionally impaired and that the abnormal regulatory functions of these cells can be analysed by [Ca2+<\/jats:sup>]i<\/jats:sub> following TCR<\/jats:styled-content> engagement. Furthermore, the impaired functioning of Tregs<\/jats:sub> evident in patients with asthma may be due to a high level of RACK<\/jats:styled-content>1.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cea.12375","type":"journal-article","created":{"date-parts":[[2014,7,22]],"date-time":"2014-07-22T10:15:10Z","timestamp":1406024110000},"page":"1154-1169","source":"Crossref","is-referenced-by-count":11,"title":["Elevated receptor for activated C kinase 1 expression is involved in intracellular Ca2+<\/sup> influx and potentially associated with compromised regulatory T cell function in patients with asthma"],"prefix":"10.1111","volume":"44","author":[{"given":"T.","family":"Negoro","sequence":"first","affiliation":[{"name":"Department of Pharmacogenomics Showa University School of Pharmacy Shinagawa\u2010ku Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology Showa University School of Pharmacy Shinagawa\u2010ku Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Narushima","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Showa University Northern Yokohama Hospital Yokohama city Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. H.","family":"Banham","sequence":"additional","affiliation":[{"name":"NDCLS Radcliffe Department of Medicine University of Oxford John Radcliffe Hospital Oxford OX3 9DU UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Wakabayashi","sequence":"additional","affiliation":[{"name":"Department of Pharmacogenomics Showa University School of Pharmacy Shinagawa\u2010ku Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Takayanagi","sequence":"additional","affiliation":[{"name":"Department of Pharmacogenomics Showa University School of Pharmacy Shinagawa\u2010ku Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Hagiwara","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition Science Sagami Women's Junior College Sagamihara City Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Roncador","sequence":"additional","affiliation":[{"name":"Monoclonal Antibodies Unit Biotechnology Program Centro Nacional de Investigaciones Oncologicas (CNIO) Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Osabe","sequence":"additional","affiliation":[{"name":"Department of Pharmacogenomics Showa University School of Pharmacy Shinagawa\u2010ku Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Yanai","sequence":"additional","affiliation":[{"name":"Department of Pharmacogenomics Showa University School of Pharmacy Shinagawa\u2010ku Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Kin","sequence":"additional","affiliation":[{"name":"Department of Pharmacogenomics Showa University School of Pharmacy Shinagawa\u2010ku Tokyo 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