Regulation of macrophages polarization by neutrophils: implication in tuberculosis and cancer pathology
| Project/Area Number |
17K08659
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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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| Research Field |
Pathological medical chemistry
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| Research Institution | Kyoto University |
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Principal Investigator |
Mizutani Tatsuaki 京都大学, ウイルス・再生医科学研究所, 助教 (50701843)
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| Co-Investigator(Kenkyū-buntansha) |
杉田 昌彦 京都大学, ウイルス・再生医科学研究所, 教授 (80333532)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 慢性炎症 / 好中球 / マクロファージ / がん / 免疫学 / 結核 / 慢性炎症病態 / S100 / 感染症 / 癌 |
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| Outline of Final Research Achievements |
After tuberculosis infection, the granuloma formed with heterogeneously activated macrophages. We have specified S100A9-expressing neutrophils were adjacent to immunosuppressive M2 macrophages in the granulomas. This observation suggested that S100A9/neutrophils motivated the M2 polarization in macrophages. To reveal this novel macrophage polarization pathway more explicitly, we generated S100A9 knockout （A9KO）mice and analyzed the BCG infection model as well as tumor xenograft model. Results obtained from A9KO studies revealed that the neutrophil-derived S100A9 could induce the M2 polarization in macrophages. Molecular analyses also specified that S100A9 upregulated anti-inflammatory cytokines followed by M2 macrophages polarization, which was critical for tuberculosis pathology. Besides, we noticed that less significant lung metastatic potential in A9KO compared to WT mice. These results potentially emphasize that S100A9 dependent M2 polarization could operate in the metastasis.
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| Academic Significance and Societal Importance of the Research Achievements |
炎症反応を抑制するM2マクロファージは、慢性炎症やがんの発症に深く関わるが、その誘導機序は不明な点が多い。本研究は、癌病態を宿主免疫系と癌との慢性共存状態と捉え、細菌の持続感染病態で得られた好中球によるマクロファージのM2誘導メカニズムを追求し、その分子基盤の一端を明らかにした。好中球に着目した炎症抑制機序はこれまでよく知られておらず、本研究成果の学術的意義は大きい。また、癌病態におけるM2誘導機序の解明は、新たながん治療を開発するために重要な知見となり得る。
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Report
(4 results)
Research Products
(2 results)
