| Project/Area Number |
25461015
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Gastroenterology
|
|---|
| Research Institution | Aichi Medical University (2015-2016)
Fujita Health University (2014)
Kansai Medical University (2013) |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2013-04-01 – 2017-03-31
|
| Project Status |
Completed (Fiscal Year 2016)
|
| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
|
|---|
| Keywords | PBC / IL-12 / IL-17 / サイトカイン / 原発性胆汁性肝硬変 / 自己免疫 / 肝繊維化 / 国際情報交換 アメリカ 中国 |
|---|
| 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.
|
