| Project/Area Number |
18K07186
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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 49070:Immunology-related
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| Research Institution | Nagoya University (2019-2020)
Institute of Physical and Chemical Research (2018) |
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Principal Investigator |
SEO Wooseok 名古屋大学, 医学系研究科, 特任准教授 (40574116)
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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 |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | CCL5 / Enhancer / Cancer / がん免疫 / ケモカイン / 転写制御 / Chemokine |
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| Outline of Final Research Achievements |
CCL5 is an important inflammatory chemokine and used to recruit immune cells to the infected sites to clear pathogens. Recent studies have suggested that CCL5 also functions to maintain tissue-resident immune cells within local tissues,
thus implying that CCL5 can function under both inflammatory and non-inflammatory situations.
During the thorough examination to decipher the detailed molecular regulatory circuit responsible for the specific expression of CCL5 in both inflammatory and non-inflammatory situations, I discovered that previously unknown two transcriptional enhancers, each of which is responsible for the expression of CCL5 in inflammatory and non-inflammatory situations. By the generation two gene-modified mouse lines in which either of enhancer is knocked out, I concluded that these two enhancers gives the temporal specificity of CCL5 expression by mediating chromatin loop between them.
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| Academic Significance and Societal Importance of the Research Achievements |
多くの癌組織には大量のCCL5が含まれていますが、その生理学的意味は明確に定義されておらず、CCL5を利用した効果的な治療アプローチの開発に障害になっています。私の研究は、CCL5発現調節の分子機構を解明するだけではなく、癌組織におけるCCL5存在の免疫学的意味にも新たな光を当てました。この研究成果として発表した私の論文は、がんの増殖を後押しする、CCL5の新しい役割を提供しました。この発見は、CCL5の役割に関するパラダイムシフトをもたらし、癌の治療アプローチをさらに発展させると考えています。
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