2013 Fiscal Year Final Research Report
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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| 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 |
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| 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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Author(s)
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Journal Title
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Author(s)
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