| First Author | Iizuka M | Year | 2015 |
| Journal | J Immunol | Volume | 194 |
| Issue | 1 | Pages | 56-67 |
| PubMed ID | 25411202 | Mgi Jnum | J:230700 |
| Mgi Id | MGI:5763553 | Doi | 10.4049/jimmunol.1401118 |
| Citation | Iizuka M, et al. (2015) A crucial role of RORgammat in the development of spontaneous Sialadenitis-like Sjogren's syndrome. J Immunol 194(1):56-67 |
| abstractText | The nuclear receptor retinoic acid-related orphan receptor (ROR)gammat is required for the generation of Th17 cells, which are involved in various autoimmune diseases, including Sjogren's syndrome (SS). However, the pathological role of RORgammat in SS remains to be elucidated. The present study was designed to clarify the role of RORgammat in the pathogenesis of sialadenitis-like SS. Histological analysis of RORgammat 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. RORgammat-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 RORgammat-overexpressed CD4(+) T cells and reduced Treg cells might contribute to the development of SS-like sialadenitis. |
