| Project/Area Number |
25670548
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
General surgery
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| Research Institution | Hokkaido University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
GOTO Ryoichi 北海道大学, 北海道大学病院, 医員 (10645287)
AOYAGI Takeshi 北海道大学, 北海道大学病院, 医員 (90374347)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 移植免疫 / 免疫抑制性 / 細胞治療 / 分子標的 / 免疫抑制性細胞 |
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| Outline of Final Research Achievements |
In this study, we performed basic researches on immunoregulatory cells in order to search for new immunosuppressive strategies. We found that tolerogeneic dendritic cells (tDCs) were successfully generated ex-vivo by suppressing activation of either NF-κB or MAPKs in the presence of donor-peptide antigens, and that administration of these tDCs significantly prolonged allograft survival in mice. The inhibition of NF-κB, MAPKs or AP-1/mTOR/p70S6K activation following infusion of donor-leukocytes exerted a potent immunosuppressive effect. In some of these protocols, regulatory T cells (Tregs) were effectively induced in vivo. Coculture of peripheral blood mononuclear cells and allo-antigens together with either CD80/86- or CD40-costimulation blockers induced antigen-specific Tregs that seemed to have a potential utility for clinical immunosuppression.
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