Regulatory mechanisms controlling CCL5 chemokine to maintain tissue homeostasis

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07186
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49070:Immunology-related
• Research Institution: Nagoya University (2019-2020); Institute of Physical and Chemical Research (2018)
• Principal Investigator: SEO Wooseok 名古屋大学, 医学系研究科, 特任准教授 (40574116)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: CCL5 / Enhancer / Cancer

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.

Free Research Field

がん免疫

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。