title: A crucial role of RORγt in the development of spontaneous Sialadenitis-like Sjögren's syndrome.
abstract: The nuclear receptor retinoic acid-related orphan receptor (ROR)γt is required for the generation of Th17 cells, which are involved in various autoimmune diseases, including Sjögren's syndrome (SS). However, the pathological role of RORγt in SS remains to be elucidated. The present study was designed to clarify the role of RORγt in the pathogenesis of sialadenitis-like SS. Histological analysis of RORγt transgenic (Tg) mice was determined, and then Tg mice developed severe spontaneous sialadenitis-like SS. The analysis of infiltrating cells showed that most infiltrating cells were CD4(+) T cells. RORγt-overexpressing CD4(+) T cells induced sialadenitis as a result of transferred CD4(+) T cells from Tg mice into Rag2(-/-) mice. The examination of IL-17-deficient Tg mice indicated that IL-17 was not essential for the development of sialadenitis. The number of CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells was significantly decreased in Tg mice, and CD25 expression and IL-2 stimulated STAT5 activation were inhibited in Treg cells. The inhibitory function of Treg cells of Tg mice was equal to that of wild-type mice in vitro. The abundant Treg cells of Tg mice could suppress the development of sialadenitis, but the reduced Treg cells of Tg mice could not inhibit the induction of sialadenitis in Rag2(-/-) mice transferred with effector cells from Tg mice. These results suggest that both RORγt-overexpressed CD4(+) T cells and reduced Treg cells might contribute to the development of SS-like sialadenitis.
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-0006, Japan;
authors.forename: Mana
authors.initials: M
authors.lastname: Iizuka
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-0006, Japan;
authors.forename: Hiroto
authors.initials: H
authors.lastname: Tsuboi
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-0006, Japan;
authors.forename: Naomi
authors.initials: N
authors.lastname: Matsuo
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-0006, Japan;
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Asashima
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-0006, Japan;
authors.forename: Tomoya
authors.initials: T
authors.lastname: Hirota
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-0006, Japan;
authors.forename: Yuya
authors.initials: Y
authors.lastname: Kondo
authors.affiliation: Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Chiba 278-0022, Japan; and.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.affiliation: Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-0006, Japan;
authors.forename: Isao
authors.initials: I
authors.lastname: Matsumoto
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-0006, Japan; tsumida@md.tsukuba.ac.jp.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Sumida
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000276:immunology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D020381:Interleukin-17 / Q000235:genetics; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D008168:Lung / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000096:biosynthesis*; D050799:STAT5 Transcription Factor / Q000096:biosynthesis*; D012463:Saliva / Q000502:physiology; D012469:Salivary Glands / Q000502:physiology; D012793:Sialadenitis / Q000276:immunology*; D012859:Sjogren's Syndrome / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D020381:Interleukin-17; D053645:Interleukin-2 Receptor alpha Subunit; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C499308:Rag2 protein, mouse; D050799:STAT5 Transcription Factor