Expression of signal-transducing adaptor protein-1 attenuates experimental autoimmune hepatitis via down-regulating activation and homeostasis of invariant natural killer T cells

Kashiwakura, Jun-ichi; Saitoh, Kodai; Ihara, Takeru; Sasaki, Yuto; Kagohashi, Kota; Enohara, Shiyo; Morioka, Yuka; Watarai, Hiroshi; Muromoto, Ryuta; Kitai, Yuichi; Iwabuchi, Kazuya; Oritani, Kenji; Matsuda, Tadashi

Expression of signal-transducing adaptor protein-1 attenuates experimental autoimmune hepatitis via down-regulating activation and homeostasis of invariant natural killer T cells

Kashiwakura, Jun-ichi; Saitoh, Kodai; Ihara, Takeru et al.

PLoS ONE, 2020, 15(11), e0241440

Permalink : https://hdl.handle.net/2115/80133

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アクセス権	open access
URI	https://hdl.handle.net/2115/80133
タイトル	Expression of signal-transducing adaptor protein-1 attenuates experimental autoimmune hepatitis via down-regulating activation and homeostasis of invariant natural killer T cells
著者	Kashiwakura, Jun-ichi ; Saitoh, Kodai ; Ihara, Takeru ; Sasaki, Yuto ; Kagohashi, Kota ; Enohara, Shiyo ; Morioka, Yuka ; Watarai, Hiroshi ; Muromoto, Ryuta ; Kitai, Yuichi ; Iwabuchi, Kazuya ; Oritani, Kenji ; Matsuda, Tadashi
e-Rad_Researcher 90373290 著者名 Kashiwakura, Jun-ichi
著者名 Saitoh, Kodai
著者名 Ihara, Takeru
著者名 Sasaki, Yuto
著者名 Kagohashi, Kota
著者名 Enohara, Shiyo
著者名 Morioka, Yuka
著者名 Watarai, Hiroshi
e-Rad_Researcher 30455597 著者名 Muromoto, Ryuta
e-Rad_Researcher 90756165 著者名 Kitai, Yuichi
著者名 Iwabuchi, Kazuya
著者名 Oritani, Kenji
e-Rad_Researcher 20212219 著者名 Matsuda, Tadashi
言語	英語
発行日	2020-11-11
出版者	PLOS
収録物名	PLoS ONE
巻(号)	15(11)
ページ	e0241440
抄録	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.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
権利情報	Creative Commons Attribution 4.0 International
PISSN	1932-6203
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.1371/journal.pone.0241440