2023 Fiscal Year Final Research Report
Development of an innovative cell transplantation therapy using CD8 regulatory T cells to induce immune tolerance after organ transplantation
| Project/Area Number |
21K08615
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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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| Review Section |
Basic Section 55010:General surgery and pediatric surgery-related
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| Research Institution | Shinshu University |
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Principal Investigator |
Notake Tsuyoshi 信州大学, 学術研究院医学系(医学部附属病院), 助教 (40645511)
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| Co-Investigator(Kenkyū-buntansha) |
清水 明 信州大学, 学術研究院医学系(医学部附属病院), 准教授 (00447773)
窪田 晃治 信州大学, 学術研究院医学系(医学部附属病院), 講師 (10598220)
副島 雄二 信州大学, 学術研究院医学系, 教授 (30325526)
増田 雄一 信州大学, 学術研究院医学系(医学部附属病院), 准教授 (60467149)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | 移植免疫 / Kupffer細胞 |
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| Outline of Final Research Achievements |
The transcription factor IRF2-dependent Ly49 T cells which we found in our previous study had a different phenotype from previously reported CD8 positive inhibitory T cells (CD8 Tregs). We had planned to evaluate the function of CD8 Tregs using an ex vivo TFH-stimulated mice model using peptides, but we were unable to establish this model. For this reason, we gave up on developing a cell transfer therapy to induce immune tolerance using CD8 Tregs, and instead changed our approach to investigating other immune cells in the liver that may affect the rejection reaction after liver transplantation.
We focused on Kupffer cells (F4/80hiCD11b+Tim4+) in the liver and investigated the effects of IRF2 on this population. We found that external stimulation by IFNγ and the action of cell intrinsic IRF2 are necessary for Kupffer cells to express MHC class II.
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| Free Research Field |
消化器外科学
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| Academic Significance and Societal Importance of the Research Achievements |
Kupffer細胞分化のmechanismを解明することは、肝臓局所での免疫応答、つまり肝移植後の拒絶反応や腫瘍に対する免疫応答、肝臓における発がんの病態解明につながる可能性がある。
今回我々は、Kupffer細胞上のMHC classII発現には肝臓局所におけるIFNγの存在と、同細胞内でのIRF2の働きが重要であることを解明した。Kupffer細胞が肝臓局所において免疫抑制状態の誘導に重要な役割を果たしていることが報告されている。この知見をもとに、IRF2を介した免疫制御やIRF2発現の程度による拒絶のリスク評価などへの臨床応用が期待される。
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