Development of novel therapeutic strategy against neurodegenerative diseases by modulation of monocyte-lineage cell
| Project/Area Number |
18K07531
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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 52020:Neurology-related
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| Research Institution | Yokohama City University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
土井 宏 横浜市立大学, 医学部, 准教授 (10326035)
田中 章景 横浜市立大学, 医学研究科, 教授 (30378012)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 単球系細胞 / ミクログリア / マクロファージ / アストロサイト / 神経炎症 / IL-19 / 神経変性疾患 |
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| Outline of Final Research Achievements |
IL-19 acts as a negative-feedback regulator to limit proinflammatory response of macrophages/microglia. We showed that IL-19 deficiency aggravates EAE and IL-19-treatment significantly abrogated it. IL-19 suppresses MS pathogenesis by inhibiting macrophage antigen presentation. IL-19-deficient SOD1 Tg mice exhibited significant improvement of motor function accompanied by upregulating microglial TNF-α and subsequent astrocytic GDNF, indicating that inhibition of IL-19 signaling may alleviate ALS symptoms. Then, we generated CX3CR1/CCR2-reporter SOD1 Tg mice that enables distinction between microglia and CNS infiltrating macrophage. We found that microglia and neurons partially expressed CCR2, but not astrocytes, associated with an increase in CNS infiltrating CCR2+ macrophage as disease progression, suggesting that macrophage CNS infiltration leads to CNS environmental deterioration due to toxic conversion of microglia and neurons.
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| Academic Significance and Societal Importance of the Research Achievements |
単球系細胞のネガティブフィードバック因子であるIL-19が、神経免疫疾患や神経変性疾患といった病態の違いに応じて、神経保護作用・神経障害作用の二面性を示しうることを明らかにした。また、ALSモデルマウスの病勢進行に伴ったCCR2陽性単球の中枢神経浸潤の増加と、ミクログリアや神経細胞におけるCCR2の発現誘導が、神経炎症の悪循環を惹起し、ALSの病態形成の一機序を担っている可能性を示した。
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Report
(4 results)
Research Products
(8 results)
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[Journal Article] CCR2 is localized in microglia and neurons, as well as infiltrating monocytes, in the lumbar spinal cord of ALS mice.2020
Author(s)
Komiya H, Takeuchi H (責任著者), Ogawa Y, Hatooka Y, Takahashi K, Katsumoto A, Kubota S, Nakamura H, Kunii M, Tada M, Doi H, Tanaka F
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Journal Title
Molecular Brain
Volume: 13
Issue: 1
Pages: 64-64
DOI
Related Report
Peer Reviewed / Open Access
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