2019 Fiscal Year Research-status Report
Regulatory mechanisms controlling CCL5 chemokine to maintain tissue homeostasis
| Project/Area Number |
18K07186
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| Research Institution | Nagoya University |
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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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| Keywords | がん免疫 / ケモカイン / 転写制御 |
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| Outline of Annual Research Achievements |
CCL5 has been known as an inflammatory chemokine to fight infections by recruiting immune cells to the infected sites. However, recent researches suggested that it could also function to maintain the homeostasis of tissue-resident immune cells by maintaining them within local tissues.
In this research project, I proposed to find the molecular mechanisms and physiological significance of this new regulatory role of CCL5 during tissue homeostasis by expending my previous researches in which I characterized the transcriptional regulation of CCL5. During the first fiscal year of this research proposal, I discovered that the expression of CCL5 is elaborately regulated by previously unidentified two transcriptional enhancers by using mouse knockout models.
During the second year of this research proposal, I examined the functional significance of these two enhancers by using mouse cancer models. I found that CCL5 released from host immune cells contributes to the cellular activities of the cells thus influencing their cancer-fighting properties. Eventually, I discovered that CCL5 secreted from host immune cells can function as a pro-cancer molecule since model mice attacked cancer more efficiently without host CCL5. These results were published in a peer reviewed journal.
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| Current Status of Research Progress |
Current Status of Research Progress
1: Research has progressed more than it was originally planned.
Reason
The goal of this second year was to decipher and investigate the physiological role of the new transcriptional enhancers of CCL5 I characterized during the first year of the research proposal. I successfully achieved this goal by finding that CCL5 expressed from host cells unexpectedly plays a pro-cancer role with mouse cancer models. Since CCL5 chemokine from hosts has been presumed to function as an anti-cancer molecule to protect hosts from cancer, my discovery suggests a previously unappreciated role of CCL5 during tumorigenesis. Furthermore, I was able to publish this result at a peer-reviewed journal during the current fiscal year. Therefore, I will be able to accomplish the third goal of this research proposal within the planned time schedule.
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| Strategy for Future Research Activity |
My discovery that CCL5 from hosts can play a pro-cancer role is a quite provocative and unexpected novel finding and thus it might provide important mechanistic insights for chemokine-dependent tumorigenesis. Also, this finding can be applied to devise and develop new clinical approaches to treat cancers. Especially, peer investigators and reviewers of the paper I published have provided several interesting and important suggestions which could bring this discovery to more practical applications. Thus, I plan to characterize the mechanism by which CCL5 functions as pro-cancer molecules. I will examine immune cells within cancer micro-environments in the absence of CCL5 expression by using the knockout mice of CCL5 enhancers I generated.
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| Causes of Carryover |
購入を予定していたサイトカンとケモカインの購入費が少なく、学会参加費が不要であったため、31年度の研究費に未使用額が生じた。令和2年度は予定しなかった謝金が必要なので、研究計画に変更は必要なく、当初予定通りの計画を進めていく。
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