Immune mechanisms involved in the development of fatal autoimmune hepatitis in mice
| Project/Area Number |
23590973
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Kyoto University |
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Principal Investigator |
WATANABE Norihiko 京都大学, 医学(系)研究科(研究院), 非常勤講師 (50419446)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 内科学 / 肝臓病学 / 免疫学 / 劇症肝炎 / 自己免疫性肝炎 / 消化管免疫 / サイトカイン / ケモカイン |
|---|
| Research Abstract |
Some of the patients with autoimmune hepatitis (AIH) manifest liver failure at initial presentation. However, it is unknown how the progression to fulminant hepatitis occurs. We developed a mouse model of fulminant AIH by inducing a concurrent loss of Foxp3+ regulatory T cells and PD-1-mediated signaling. During AIH progression in these mice, T-bet together with IFN-gamma and CXCR3 were highly expressed in the inflamed liver, and T cells in the spleen and inflamed liver dominantly expressed CXCR3. Expression of one CXCR3 ligand, CXCL9, was elevated in the liver; in vivo administration of anti-CXCL9 suppressed AIH progression. In addition, serum levels of IL-18 were elevated during progression, and dendritic cells in the spleen and liver highly produced IL-18. In vivo administration of anti-IL-18R suppressed the increase of splenic CXCR3+ T cells and the fatal progression of hepatitis. These data suggest that in our model, IL-18 is critical for the progression to fulminant hepatitis.
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Report
(4 results)
Research Products
(43 results)
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[Journal Article] Long-term clinical outcome of gastric MALT lymphoma after eradication of Helicobacter pylori : a multicentre cohort follow-up study of 420 patients in Japan2012
Author(s)
Nakamura S, Sugiyama T, Matsumoto T, Iijima K, Ono S, Tajika M, TariA, Kitadai Y, Matsumoto H, Nagaya T, Kamoshida T, Watanabe N, Chiba T, Origasa H, Asaka M; for the JAPAN GAST Study Group
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Journal Title
Gut
Volume: 61
Issue: 4
Pages: 507-513
DOI
NAID
Related Report
Peer Reviewed
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[Journal Article] Primary gastrointestinal follicular lymphoma involving the duodenal second portion is a distinct entity : a multicenter, retrospective analysis in Japan2011
Author(s)
Takata K, Okada H, Ohmiya N, Nakamura S, Kitadai Y, Tari A, Akamatsu T, Kawai H, Tanaka S, Araki H, Yoshida T, Okumura H, Nishisaki H, Sagawa T, Watanabe N, Arima N, Takatsu N, Nakamura M, Yanai S, Kaya H, Morito T, Sato Y, Moriwaki H, Sakamoto C, Niwa Y, Goto H, Chiba T, Matsumoto T, Ennishi D, Kinoshita T, Yoshino T
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Journal Title
Cancer Sci
Volume: 102
Pages: 1532-1536
NAID
Related Report
Peer Reviewed
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[Journal Article] Dys-regulated generation of follicular helper T cells in the spleen triggers fatal autoimmune hepatitis in mice2011
Author(s)
N. Aoki, M. Kido, S. Iwamoto, H. Nishiura, R. Maruoka, J. Tanaka, T. Watanabe, Y. Tanaka, T. Okazaki, T. Chiba, N. Watanabe
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Journal Title
Gastroenterology
Volume: vol.140, No.4
Issue: 4
Pages: 1322-1333
DOI
Related Report
Peer Reviewed
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