| First Author | Kashiwakura JI | Year | 2020 |
| Journal | PLoS One | Volume | 15 |
| Issue | 11 | Pages | e0241440 |
| PubMed ID | 33175848 | Mgi Jnum | J:298913 |
| Mgi Id | MGI:6473635 | Doi | 10.1371/journal.pone.0241440 |
| Citation | Kashiwakura JI, et al. (2020) Expression of signal-transducing adaptor protein-1 attenuates experimental autoimmune hepatitis via down-regulating activation and homeostasis of invariant natural killer T cells. PLoS One 15(11):e0241440 |
| abstractText | 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. |
