2016 Fiscal Year Final Research Report
Mechanism of hepatic fibrosis and cytokines in primary biliary cirrhosis (PBC).
| Project/Area Number |
25461015
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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 | Aichi Medical University (2015-2016)
Fujita Health University (2014)
Kansai Medical University (2013) |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2017-03-31
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| Keywords | PBC / IL-12 / IL-17 / サイトカイン |
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| Outline of Final Research Achievements |
Increased expression levels of IFN-g and increased frequency of IL-17-producing lymphocytes in liver tissues had been reported from patients with primary biliary cirrhosis.
In the present study, mice are immunized with 2OA-BSA, to test the hypothesis that IL-17 potentiates Th1-mediated autoimmune cholangitis induced by 2OA-BSA immunization. A complete suppression of cholangitis manifestations, including production of antimitochondrial autoantibodies, portal inflammation, bile duct damage and granuloma formation, was observed in either IL-12p40 or IFN-g deficiency mice, but not in IL-17 deficiency mice immunized with 2OA-BSA. While deletion of IL-17 significantly reduced portal cellular infiltrates and bile duct damage and decreased production of antimitochondrial autoantibodies (AMA) at eight weeks after 2OA-BSA immunization. These data suggest that autoimmune cholangitis requires activation of the IL-12/IFN-g pathway and IL-17 potentiates IL-12/IFN-g-mediated autoimmunity.
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| Free Research Field |
免疫
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