RORγt antagonist improves Sjögren's syndrome‐like sialadenitis through downregulation of CD25
| العنوان: | RORγt antagonist improves Sjögren's syndrome‐like sialadenitis through downregulation of CD25 |
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| المؤلفون: | Seiji Nakamura, Satoru Takahashi, Masafumi Moriyama, Hanae Kudo, Hiroyuki Takahashi, Isao Matsumoto, Hiroto Tsuboi, Yuya Kondo, Fumika Honda, Saori Abe, Takayuki Sumida, Hiromitsu Asashima, Yuko Ono |
| المصدر: | Oral Diseases. 26:766-777 |
| بيانات النشر: | Wiley, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | CD4-Positive T-Lymphocytes, Saliva, Aminopyridines, Down-Regulation, Mice, Transgenic, chemical and pharmacologic phenomena, Salivary Glands, Sialadenitis, Mice, 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, RAR-related orphan receptor gamma, medicine, Animals, Humans, IL-2 receptor, General Dentistry, Sulfonamides, Chemistry, CD69, Interleukin-2 Receptor alpha Subunit, FOXP3, hemic and immune systems, 030206 dentistry, Nuclear Receptor Subfamily 1, Group F, Member 3, medicine.disease, Molecular biology, Mononuclear cell infiltration, Sjogren's Syndrome, Otorhinolaryngology, 030220 oncology & carcinogenesis |
| الوصف: | Objective We reported previously that T-cell-specific RORγt-transgenic mice under human CD2 promoter (RORγt-Tg mice) developed severe spontaneous Sjogren's syndrome (SS)-like sialadenitis, induced by RORγt-overexpressing CD4+ T cells and reduced regulatory T cells. The purpose of this study was to clarify the effectiveness and mechanisms of action of A213, a RORγt antagonist, in RORγt-Tg mice with SS-like sialadenitis. Methods Six-week-old RORγt-Tg mice were administered orally of A213 or phosphate-buffered saline every 3 days for 2 weeks. 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+ CD25+ Foxp3- and CD4+ CD25+ Foxp3+ cells in cLNs. We also investigated in vitro the potential immunomechanisms of action of A213. Results 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+ CD25+ /CD4+ T cells and the protein expression levels of CD69 on CD4+ CD25+ Foxp3- cells. In vitro experiments showed that A213 suppressed CD25 expression on CD4+ T cells and reduced IL-2 production from CD4+ T cells derived from RORγt-Tg mice. Conclusion A213 improves SS-like sialadenitis through the inhibition of CD4+ CD25+ cells in cLNs. |
| تدمد: | 1601-0825 1354-523X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2a4925c7488f01d53eafb36a177a61a6Test https://doi.org/10.1111/odi.13255Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2a4925c7488f01d53eafb36a177a61a6 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16010825 1354523X |
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