Analysis of Therapeutic Potential of Monocytic Myeloid-derived Suppressor Cells in Cardiac Allotransplantation
| Project/Area Number |
19K18070
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 55010:General surgery and pediatric surgery-related
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| Research Institution | Juntendo University |
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Principal Investigator |
Uchida Koichiro 順天堂大学, 健康総合科学先端研究機構, 准教授 (80648329)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 移植 / 拒絶反応 / 細胞治療 / 骨髄由来抑制性細胞 / ミエロイド系抑制細胞 / 移植免疫 / 免疫寛容 |
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| Outline of Research at the Start |
抑制系細胞の“記憶維持”すなわち免疫寛容の維持機構を解明に挑戦する。 本研究では、癌の免疫回避機構やアレルギーの制御機構など抹消性(局所)の免疫寛容を誘導するミエロイド系抑制細胞 (myeloid derived suppressor cells: MDSC)に注目し、マウス異所性心移植のアロ移植免疫寛容モデル(CD80/86抗体投与)を用いて、移植片の寛容状態にMDSCがどのように貢献しているかを検討する。 さらに、申請者らが研究開発したin vitro誘導性のMDSC、中でも抑制能や制御性T細胞の誘導能の高い単球系MDSCを今回より効率よく培養誘導する技術基盤を構築する。
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| Outline of Final Research Achievements |
Syngeneic and allogeneic bone marrow-derived MDSCs (BM-MDSCs) were induced and their effect on graft survival and suppressive capacity were analyzed. Moreover, we compared the ability of syngeneic monocytic MDSCs (Mo-MDSCs) and polymorphonuclear MDSCs (PMN-MDSCs) to inhibit graft rejection and analyze the mechanisms of suppression.
Results Not only syngeneic but also allogeneic donor- or allogeneic third party-derived BM-MDSCs prolonged graft survival, although syngeneic BM-MDSCs inhibited anti-donor immune responses most effectively in vitro. Mo-MDSCs, rather than PMN-MDSCs, were responsible for immune suppression through inducible nitric oxide synthase (iNOS), and expanded naturally occurring thymic originated Treg (nTreg) in vitro. Adoptive transfer of Mo-MDSCs, but not PMN-MDSCs, prolonged graft survival and increased Treg infiltration into the graft heart.
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| Academic Significance and Societal Importance of the Research Achievements |
単球系の骨髄由来抑制細胞のターゲットとした新たな免疫抑制治療の効果メカニズムが解明された。これらにより、副作用の強い薬剤の全身投与ではなく、抑制性細胞治療という炎症部位を選択的に制御できる方法論の治療コンセプトを確立することができた。
この細胞療法は、制御性T細胞治療のように、レシピエントのMHCを合わせなくても、投与可能であり、効果を発揮する。また骨髄細胞は、比較的容易に採取可能であり、将来の安定供給可能な体制を構築しやすい。
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Report
(4 results)
Research Products
(2 results)
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[Journal Article] Analysis of therapeutic potential of monocytic myeloid-derived suppressor cells in cardiac allotransplantation.2021
Author(s)
Keiichi Fujimoto, Koichiro Uchida, EnzhiYin, Jun Zhu, Yuko Kojima, Masateru Uchiyama, Yasuto Yamamoto, Hisashi Bashuda, Ryu Matsumoto, Koji Tokushige, Masaki Harada, Takenori Inomata, Jiro Kitaura, Akira Murakami, Ko Okumura, Kazuyoshi Takeda.
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Journal Title
Transplant Immunology
Volume: 67
Pages: 101405-101405
DOI
Related Report
Peer Reviewed / Open Access
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