| Project/Area Number |
23K09134
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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 57020:Oral pathobiological science-related
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
張 晨陽 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (40768363)
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| Project Period (FY) |
2023-04-01 – 2026-03-31
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| Project Status |
Granted (Fiscal Year 2023)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2025: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2024: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2023: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | ILDR2 / EAE |
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| Outline of Research at the Start |
ILDR2/augulin-3は、上皮細胞の３点結合に関わる Angulin family分子として発見され、その後、共刺激分子B7 family に属し、T細胞の免疫制御に関わっていることが報告されたが、その発現分布がかなり限定されていること、 T細胞上のカウンターレセプターが同定されていないことなどから、免疫応答におけるその機能は不明な点が多い。本研究では、新規免疫チェックポイント分子 ILDR2の発現制御とその機能について、恒常的発現が見られる中枢神経系に焦点をおいて、神経免疫学的な観点から ILDR2の機能を解析する。
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| Outline of Annual Research Achievements |
In this study, we investigated the expression profile of a novel B7 checkpoint molecule, ILDR2, and applied various mouse models to clarify the immunological functions of ILDR2 in cancer immunity and neuroimmunity. We aim to deepen our understanding of new immune tolerance induction mechanisms, explore the possibility of systemic immune regulation and develop novel immunotherapy for cancer and autoimmune diseases.By using of experimental autoimmune encephalomyelitis (EAE), a mouse model of MS, the applicant and colleagues has demonstrated that the development of Eomes+ Th cells, which are closely related to disease severity of chronic EAE and SPMS patients, are largely depended on disease associated microglia (DAM)
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| Current Status of Research Progress |
Current Status of Research Progress
3: Progress in research has been slightly delayed.
Reason
We have not yet evaluated the role of ILDR2 in EAE.
That is a key part to explore the function of ILDR2 in systemic immune regulation and to develop novel immunotherapy for cancer and autoimmune diseases.
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| Strategy for Future Research Activity |
We will examine whether administration of ILDR2-Fc into EAE mice could ameliorate disease progress. In addition, we will also evaluate whether disease progression will be accelerated by administration of the neutralizing antibody against ILDR2 into EAE mice. Moreover, the interaction between microglia or astrocyte and Th cells derived from CNS can be evaluated. To evaluate the antigen-specific inhibition of ILDR2, 2D2 TCR transgenic mice that express a myelin oligodendrocyte glycoprotein (MOG)-specific T cell receptor will be used.
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