| Project/Area Number |
20K16294
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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 49070:Immunology-related
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
ZHANG CHENYANG 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) |
2020-04-01 – 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: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | neurodegeneration / microglia / EAE / multiple sclerosis / Multiple Sclerosis |
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| Outline of Research at the Start |
Effective therapies targeting at SP-MS are still lacked due to limited knowledge of pathogenic mechanisms. This research is to figure out possible interaction between Th cells, CNS APCs and microglia under chronic inflammatory condition, providing novel insights for pathogenesis of SP-MS.
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| Outline of Final Research Achievements |
The pathological process of neurodegeneration is highly complex and mechanisms are poorly understood. Although cell autonomous neurodegeneration was the major focus of research, non-cell autonomous cues have recently come to the fore. In this study, we demonstrate that neuroimmune interaction plays an intrinsic role in the transition to Eomes+ Th cell-associated neurodegeneration during EAE. This transition is associated with the accumulation of IFN-I in the CNS and upregulation of surface marker Clec7a in microglia in parallel with the induction of pathogenic Eomes+ Th cells. Furthermore, we identified long interspersed nuclear element-1 (L1) as a prominent inducer of IFN-I from microglia and a as dominant prototypic antigen that is presented to CNS Th cells.
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| Academic Significance and Societal Importance of the Research Achievements |
今回の研究により、慢性炎症がミクログリアとEomes+ Th細胞の機能変動を誘発することが明らかになった。これらの免疫細胞の活性化は、これまで知られていなかった機能的な悪循環を引き起こし、自己抗原の異所性発現を通じて神経変性に至ることが明らかになった。本研究により、免疫細胞を介した神経変性につながる神経炎症のハブとして、ミクログリアが重要な役割を担っていることを強く示唆している。
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