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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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