{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T11:18:12Z","timestamp":1777461492124,"version":"3.51.4"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2016,10,11]],"date-time":"2016-10-11T00:00:00Z","timestamp":1476144000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,1,6]]},"abstract":"<jats:title>Summary<\/jats:title>\n               <jats:p>We showed recently that M3 muscarinic acetylcholine receptor (M3R)-reactive CD3+ T cells play a pathogenic role in the development of murine autoimmune sialadenitis (MIS), which mimics Sj\u00f6gren's syndrome (SS). The aim of this study was to determine the effectiveness and mechanism of action of retinoic acid-related orphan receptor-gamma t (ROR\u03b3t) antagonist (A213) in MIS. Splenocytes from M3R knockout (M3R\u2013\/\u2013) mice immunized with murine M3R peptide mixture were inoculated into recombination-activating gene 1 knockout (Rag-1\u2013\/\u2013) mice (M3R\u2013\/\u2013\u2192Rag-1\u2013\/\u2013) with MIS. Immunized M3R\u2013\/\u2013 mice (pretransfer treatment) and M3R\u2013\/\u2013\u2192Rag-1\u2013\/\u2013 mice (post-transfer treatment) were treated with A213 every 3 days. Salivary volume, severity of sialadenitis and cytokine production from M3R peptide-stimulated splenocytes and lymph node cells were examined. Effects of A213 on cytokine production were analysed by enzyme-linked immunosorbent assay (ELISA) and on T helper type 1 (Th1), Th17 and Th2 differentiation from CD4+ T cells by flow cytometry. Pretransfer A213 treatment maintained salivary volume, improved MIS and reduced interferon (IFN)-\u03b3 and interleukin (IL)-17 production significantly compared with phosphate-buffered saline (PBS) (P\u2009&amp;lt;\u20090\u00b705). These suppressive effects involved CD4+ T cells rather than CD11c+ cells. Post-transfer treatment with A213 increased salivary volume (P\u2009&amp;lt;\u20090\u00b705), suppressed MIS (P\u2009&amp;lt;\u20090\u00b7005) and reduced IFN-\u03b3 and IL-17 production (P\u2009&amp;lt;\u20090\u00b705). In vitro, A213 suppressed IFN-\u03b3 and IL-17 production from M3R-stimulated splenocytes and CD4+ T cells of immunized M3R\u2013\/\u2013 mice (P\u2009&amp;lt;\u20090\u00b705). In contrast with M3R specific responses, A213 suppressed only IL-17 production from Th17 differentiated CD4+ T cells without any effect on Th1 and Th2 differentiation in vitro. Our findings suggested that ROR\u03b3t antagonism is potentially suitable treatment strategy for SS-like sialadenitis through suppression of IL-17 and IFN-\u03b3 production by M3R-specific T cells.<\/jats:p>","DOI":"10.1111\/cei.12868","type":"journal-article","created":{"date-parts":[[2016,9,19]],"date-time":"2016-09-19T23:36:41Z","timestamp":1474328201000},"page":"213-224","source":"Crossref","is-referenced-by-count":16,"title":["ROR\u03b3t antagonist suppresses M3 muscarinic acetylcholine receptor-induced Sj\u00f6gren's syndrome-like sialadenitis"],"prefix":"10.1093","volume":"187","author":[{"given":"M","family":"Tahara","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"Tsuboi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Segawa","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"Asashima","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Iizuka-Koga","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T","family":"Hirota","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y","family":"Kondo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Matsui","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Fureai Higashitotsuka Hospital, Yokohama, Kanagawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T","family":"Sumida","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2016,10,11]]},"reference":[{"key":"2021120808030445000_cei12868-bib-0001","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/S0049-0172(00)80016-5","article-title":"Clinical evolution, and morbidity and mortality of primary Sj\u00f6gren's syndrome","volume":"29","author":"Skopouli","year":"2000","journal-title":"Semin Arthritis Rheum"},{"key":"2021120808030445000_cei12868-bib-0002","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1002\/acr.21610","article-title":"Primary Sj\u00f6gren's syndrome as a systemic disease: a study of participants enrolled in an international Sj\u00f6gren's syndrome 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