2020 Fiscal Year Annual Research 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 | CCL5 / Cancer / Enhancer |
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| Outline of Annual Research Achievements |
CCL5 is one of the main inflammatory chemokines which function to recruit immune cells to the infected sites to clear the disease-causing pathogens. The recent studies have suggested that CCL5 also functions to keep various kinds of tissue-resident leukocytes within local tissues, thus implying that CCL5 regulates leukocyte movement under both inflammatory and non-inflammatory situations.
To find the molecular mechanisms and physiological significance of CCL5, I attempted to decipher the detail regulatory circuit responsible for the dynamic expression patterns of CCL5 in both inflammatory and non-inflammatory situations. This research activity resulted in the previously unknown two transcriptional enhancers, each of which is responsible for the expression of CCL5 in inflammatory and non-inflammatory settings. To further characterize these enhancers, I generated two mice models in which either of enhancer is deleted from the genome by genome targeting in mice. By using these mice models, I discovered that CCL5 has a previously unappreciated roles in the maintenance of T cell activity.
This interesting discovery was tested in cancer models and further found that CCL5 function as an anti-cancer molecule. This indicates that CCL5 modulation can have an impact in further drug development against cancer. These results were published in a peer reviewed journal in 2020.
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