Construction of a innate/acquired immune spatiotemporal network to induce antigen-specific transplant immune tolerance
| Project/Area Number |
17H04277
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | National Center for Child Health and Development |
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Principal Investigator |
Rii Ko 国立研究開発法人国立成育医療研究センター, 移植免疫研究室, 室長 (60321890)
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| Co-Investigator(Kenkyū-buntansha) |
西尾 佳明 国立研究開発法人国立成育医療研究センター, RI管理室, 共同研究員 (80727347)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2020: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2019: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
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| Keywords | 免疫寛容 / 自然免疫 / 獲得免疫 / 臓器移植 / 細胞・組織 / 移植免疫 |
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| Outline of Final Research Achievements |
Current immunosuppressive therapies require the administration of permanent immunosuppressive drugs, and side effects due to unnecessary immunosuppression have become a problem. The purpose of this study is to "construct a transplant antigen-specific immunoregulatory environment in vivo and establish a transplant antigen-specific immunotolerance induction method". Using pre-transplant administration of regulatory dendritic cells, antibodies with donor antigens, zymosan, Oridonin, which is a major biologically active component of natural herbs, etc., we confirmed their effect for prolonging grafts survival days in mouse allo-cardiac transplant model. The mechanism which was constructed an antigen-specific immunoregulatory environment in vivo was analyzed. These research results suggest that the innate immunity may plays an important role for prolonging allograft survival and inducing transplantation immune tolerance.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の成果は、生体内で自然免疫を惹起する刺激を引き起こし、移植抗原特異的な免疫制御環境を構築することであり、移植抗原特異的な免疫（獲得免疫）制御機序を誘導し、免疫抑制剤投与の減少に移植免疫寛容を成り立たせることの可能性を示唆された。これら研究成果を近い将来臨床応用する際、本邦の生体移植が行われる割合が高い特徴を生かせて、移植に先んじて移植抗原の同定が可能であることから、あらかじめ同定された移植抗原を用いて、移植患者において移植臓器特異的な免疫制御機序を誘導することが可能と予想する。移植後の初期段階から少ない免疫抑制剤の投与、あるいは投与無しに移植臓器の生着を成し遂げることが可能と期待する。
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Report
(5 results)
Research Products
(20 results)
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[Journal Article] 5-Aminolevulinic acid combined with sodium ferrous citrate (5-ALA/SFC) ameliorated liver injury in a murine acute graft-versus-host disease model by reducing inflammation responses through PGC1-α activation2020
Author(s)
1.Wang ZD, K, Liu C, Hu X, Que WT, Ito H, Takahashi K, Nakajima M, Tanaka T, Ren K, Guo WZ, Yi SQ, Li XK.
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Journal Title
Drug Discoveries & Therapeutics
Volume: 14
Issue: 6
Pages: 304-312
DOI
NAID
ISSN
1881-7831, 1881-784X
Year and Date
2020-12-31
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Combination of 5-aminolevulinic acid and iron prevents skin fibrosis in murine sclerodermatous graft-versus-host disease.2018
Author(s)
Liu C, Yang X, Zhu P, Fujino M, Ito H, Takahashi K, Nakajima M, Tanaka T, Wang J, Zhuang J, Zou H, Li XK.
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Journal Title
Exp Dermatol.
Volume: 10
Issue: 10
Pages: 1104-1111
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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