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Expression of signal-transducing adaptor protein-1 attenuates experimental autoimmune hepatitis via down-regulating activation and homeostasis of invariant natural killer T cells
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Title: | Expression of signal-transducing adaptor protein-1 attenuates experimental autoimmune hepatitis via down-regulating activation and homeostasis of invariant natural killer T cells |
Authors: | Kashiwakura, Jun-ichi Browse this author →KAKEN DB | Saitoh, Kodai Browse this author | Ihara, Takeru Browse this author | Sasaki, Yuto Browse this author | Kagohashi, Kota Browse this author | Enohara, Shiyo Browse this author | Morioka, Yuka Browse this author | Watarai, Hiroshi Browse this author | Muromoto, Ryuta Browse this author →KAKEN DB | Kitai, Yuichi Browse this author →KAKEN DB | Iwabuchi, Kazuya Browse this author | Oritani, Kenji Browse this author | Matsuda, Tadashi Browse this author →KAKEN DB |
Issue Date: | 11-Nov-2020 |
Publisher: | PLOS |
Journal Title: | PLoS ONE |
Volume: | 15 |
Issue: | 11 |
Start Page: | e0241440 |
Publisher DOI: | 10.1371/journal.pone.0241440 |
Abstract: | Objective Signal-transducing adaptor protein (STAP) family members function as adaptor molecules and are involved in several events during immune responses. Notably however, the biological functions of STAP-1 in other cells are not known. We aimed to investigate the functions of STAP-1 in invariant natural killer T (iNKT) cells and iNKT cell-dependent hepatitis. Methods We employed concanavalin A (Con A)-induced hepatitis and alpha-galactosylceramide (alpha-GalCer)-induced hepatitis mouse models, both are models of iNKT cell-dependent autoimmune hepatitis, and STAP-1 overexpressing 2E10 cells to investigate the role of STAP-1 in iNKT cell activation in vivo an in vitro, respectively. Results After Con A- or alpha-GalCer-injection, hepatocyte necrotic areas and plasma alanine aminotransferase elevation were more severe in STAP-1 knockout (S1KO) mice and milder in lymphocyte-specific STAP-1 transgenic (S1Tg) mice, as compared to wild-type (WT) mice. Two events that may be related to Con A-induced and/or alpha-GalCer-induced hepatitis were influenced by STAP-1 manipulation. One is that iNKT cell populations in the livers and spleens were increased in S1KO mice and were decreased in S1Tg mice. The other is that Con A-induced interleukin-4 and interferon-gamma production was attenuated by STAP-1 overexpression. These effects of STAP-1 were confirmed using 2E10 cells overexpressing STAP-1 that showed impairment of interleukin-4 and interferon-gamma production as well as phosphorylation of Akt and mitogen-activated protein kinases in response to Con A stimulation. Conclusions These results conclude that STAP-1 regulates iNKT cell maintenance/activation, and is involved in the pathogenesis of autoimmune hepatitis. |
Rights: | https://creativecommons.org/licenses/by/4.0/ |
Type: | article |
URI: | http://hdl.handle.net/2115/80133 |
Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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