The interaction between the intestinal microbiota and hepatic macrophages in the pathogenesis of liver fibrosis
| Project/Area Number |
25860559
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Gastroenterology
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| Research Institution | Keio University |
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Principal Investigator |
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| Research Collaborator |
Kanai Takanori 慶應義塾大学, 医学部, 教授 (40245478)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 腸内細菌 / 急性肝障害 / 肝硬変 / 免疫寛容 / Toll様受容体 / マクロファージ / ケモカイン / 肝線維化 |
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| Outline of Final Research Achievements |
We report that TNFα-producing CCR9+ macrophages infiltrated during the process of CCl4-induced liver fibrosis, and CCR9 deficiency protects the liver from overt fibrosis. Liver-infiltrating CD11b+ macrophages from CCl4-treated WT mice (CCR9+ macrophages), but not CD8+ T lymphocytes or non-CD11b+ cells, showed a significantly superior ability to activate HSCs over those from CCR9-/- mice in vitro.
Following Concanavalin A administration, a murine model of acute liver injury, in addition to the accumulation of inflammatory macrophages and suppressive dendritic cells in the liver, the composition of intestinal bacterial flora such as Genus Bacteroides and Genus Lactobacillus sequentially changed. Transplantation of fecal microbiota derived from mice post-ConA administration, but not from untreated mice, to gut sterilized mice induced immunosuppressive CD11c+ cDCs in the liver and reduced liver injury by ConA.
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Report
(4 results)
Research Products
(4 results)
