Cell-autonomous migration of macrophages via interferon regulatory factor 8 is crucial for the functional recovery after spinal cord injury
| Project/Area Number |
16H05450
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Kyushu University |
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Principal Investigator |
Okada Seiji 九州大学, 生体防御医学研究所, 教授 (30448435)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2018: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2017: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2016: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
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| Keywords | 脊髄損傷 / 炎症細胞 / 反応性アストロサイト / マクロファージ |
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| Outline of Final Research Achievements |
Traumatic spinal cord injury (SCI) brings numerous inflammatory cells, including macrophages, from the circulating blood to lesions, but the fate of these cells is unknown. We herein demonstrate that macrophages actively migrate toward the lesion epicenter after SCI, depending on the gradient of chemoattractant C5a. However, macrophages lacking interferon regulatory factor 8 (IRF8) can not migrate and remain widely scattered in the injured cord, resulting in a poor pathological and functional outcome. Conversely, pharmacological IRF8 activation promoted macrophage-autonomous migration with a significant increase in the purinergic receptors expression, thereby improving the functional recovery. Our findings revealed the importance of the bidirectional interaction between infiltrating macrophages and CNS cells, providing a novel therapeutic target for CNS injury.
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| Academic Significance and Societal Importance of the Research Achievements |
中枢神経外傷に於いてはマクロファージなどの炎症細胞浸潤を認めるが、これらの浸潤してきた細胞の運命は殆ど解明されていなかった。我々は、脊髄損傷後の浸潤してきたマクロファージの能動的な移動が組織修復と運動機能回復に重要であることを見出した。この知見は中枢神経外傷に対する新しい治療戦略を提唱するのみならず、神経生理学や細胞生物学に於いても新規の知見であり、今後益々の細胞制御による病態治療研究の発展が期待されるものと考えられる。
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Report
(4 results)
Research Products
(31 results)
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[Journal Article] Periostin Promotes Scar Formation through the Interaction between Pericytes and Infiltrating Monocytes/Macrophages after Spinal Cord Injury.2017
Author(s)
Yokota K, Kobayakawa K, Saito T, Hara M, Kijima K, Ohkawa Y, Harada A, Okazaki K, Ishihara K, Yoshida S, Kudo A, Iwamoto Y, Okada S.
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Journal Title
Am J Pathol.
Volume: 187
Issue: 3
Pages: 639-653
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Experimental Mouse Model of Lumbar Ligamentum Flavum Hypertrophy.2017
Author(s)
Saito T, Yokota K, Kobayakawa K, Hara M, Kubota K, Harimaya K, Kawaguchi K, Hayashida M, Matsumoto Y, Doi T, Shiba K, Nakashima Y, Okada S.
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Journal Title
PLoS One
Volume: 6
Issue: 1
Pages: 1-15
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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