{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T10:35:22Z","timestamp":1752230122043,"version":"3.40.5"},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,3,3]],"date-time":"2020-03-03T00:00:00Z","timestamp":1583193600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oral Diseases"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>We reported previously that T\u2010cell\u2010specific ROR\u03b3t\u2010transgenic mice under human CD2 promoter (ROR\u03b3t\u2010Tg mice) developed severe spontaneous Sj\u00f6gren's syndrome (SS)\u2010like sialadenitis, induced by ROR\u03b3t\u2010overexpressing CD4<jats:sup>+<\/jats:sup>T cells and reduced regulatory T cells. The purpose of this study was to clarify the effectiveness and mechanisms of action of A213, a ROR\u03b3t antagonist, in ROR\u03b3t\u2010Tg mice with SS\u2010like sialadenitis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Six\u2010week\u2010old ROR\u03b3t\u2010Tg mice were administered orally of A213 or phosphate\u2010buffered saline every 3\u00a0days for 2\u00a0weeks. We analyzed saliva volume, histopathology of salivary glands, populations of T cells in splenocytes and cervical lymph nodes (cLNs), and the protein expression levels of CD69 on CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup>Foxp3<jats:sup>\u2212<\/jats:sup> and CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup>Foxp3<jats:sup>+<\/jats:sup> cells in cLNs. We also investigated in vitro the potential immunomechanisms of action of A213.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A213 significantly increased saliva volume, reduced mononuclear cell infiltration in salivary glands, and reduced the focus score of sialadenitis. Analysis of the immunomechanisms using cLNs showed A213 significantly reduced the proportion of CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup>\/CD4<jats:sup>+<\/jats:sup> T cells and the protein expression levels of CD69 on CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup>Foxp3<jats:sup>\u2212<\/jats:sup> cells. In vitro experiments showed that A213 suppressed CD25 expression on CD4<jats:sup>+<\/jats:sup> T cells and reduced IL\u20102 production from CD4<jats:sup>+<\/jats:sup> T cells derived from ROR\u03b3t\u2010Tg mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>A213 improves SS\u2010like sialadenitis through the inhibition of CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup> cells in cLNs.<\/jats:p><\/jats:sec>","DOI":"10.1111\/odi.13255","type":"journal-article","created":{"date-parts":[[2019,12,14]],"date-time":"2019-12-14T17:15:35Z","timestamp":1576343735000},"page":"766-777","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["ROR\u03b3t antagonist improves Sj\u00f6gren's syndrome\u2010like sialadenitis through downregulation of CD25"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0066-7342","authenticated-orcid":false,"given":"Yuko","family":"Ono","sequence":"first","affiliation":[{"name":"Department of Internal Medicine Faculty of Medicine University of Tsukuba Ibaraki Japan"},{"name":"Section of Oral and Maxillofacial Oncology Division of Maxillofacial Diagnostic and Surgical Sciences Faculty of Dental Science Kyushu University Fukuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroto","family":"Tsuboi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Faculty of Medicine University of Tsukuba Ibaraki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masafumi","family":"Moriyama","sequence":"additional","affiliation":[{"name":"Section of Oral and Maxillofacial Oncology Division of Maxillofacial Diagnostic and Surgical Sciences Faculty of Dental Science Kyushu University Fukuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiromitsu","family":"Asashima","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Faculty of Medicine University of Tsukuba Ibaraki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanae","family":"Kudo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Faculty of Medicine University of Tsukuba Ibaraki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyuki","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Faculty of Medicine University of Tsukuba Ibaraki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fumika","family":"Honda","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Faculty of Medicine University of Tsukuba Ibaraki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saori","family":"Abe","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Faculty of Medicine University of Tsukuba Ibaraki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuya","family":"Kondo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Faculty of Medicine University of Tsukuba Ibaraki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoru","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Embryology Faculty of Medicine University of Tsukuba Ibaraki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isao","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Faculty of Medicine University of Tsukuba Ibaraki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seiji","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Section of Oral and Maxillofacial Oncology Division of Maxillofacial Diagnostic and Surgical Sciences Faculty of Dental Science Kyushu University Fukuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takayuki","family":"Sumida","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Faculty of Medicine University of Tsukuba Ibaraki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,3,3]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02307"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38272"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1263"},{"key":"e_1_2_8_5_1","first-page":"3","article-title":"Sj\u00f6gren's syndrome: Mechanisms of pathogenesis involve interaction of immune and neurosecretory systems","volume":"116","author":"Fox R. 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