| Project/Area Number |
26461931
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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 |
General surgery
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| Research Institution | Nippon Medical School |
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Principal Investigator |
Ishii Eiichi 日本医科大学, 大学院医学研究科, 研究生 (00193243)
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| Co-Investigator(Kenkyū-buntansha) |
清水 章 日本医科大学, 大学院医学研究科, 大学院教授 (00256942)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 移植 / 肝臓移植 / ラット / 免疫寛容 / 拒絶反応 / 病理 / microRNA / 制御性T細胞 / 動物実験 / 免疫応答 / T細胞性拒絶反応 / 抗体関連型拒絶反応 |
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| Outline of Final Research Achievements |
In DA-to-Lewis rat liver transplantation, the progressive acute T cell- and antibody-mediated rejection developed by day 11 with irreversible graft failure. In DA-to-PVG rat liver transplantation, the transient acute T cell-mediated inflammation occurred between day 7 to day 14, but reduced on day 21 and subsided on day 100 with stable graft functions. The infiltrates in DA-PVG accepting grafts at day 7 to day 14 differed from that in DA-Lew rejecting grafts in certain features, including less infiltration by T cells and macrophages, many Foxp3+Tregs, less levels of Th1 (IL-12, IFN-γ, TNF-α) and high expression of Th2 (IL-4, IL-10) cytokines. In addition, 193 microRNAs were up-regulated or down-regulated in rejecting or accepting grafts when compared with those in normal DA liver. We concluded that the immunological reactions in grafts with rejection or long-term acceptance may be regulated by specific Th1 and Th2 cytokines and several inflammatory miRNAs.
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