Regulation of macrophage inflammation by the clock gene E4BP4

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22781
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0803:Pathology, infection/immunology, and related fields
• Research Institution: Yamaguchi University
• Principal Investigator: Yamamoto Kaoru 山口大学, 大学院医学系研究科, 助教 (30885835)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: マクロファージ / 大腸炎 / E4BP4

Outline of Final Research Achievements

Circadian rhythms and disease are closely related, and it is known that shift workers whose circadian rhythms are easily disrupted have an increased incidence of lifestyle-related diseases and inflammatory diseases. Therefore, circadian rhythm research is expected to lead to disease prevention and treatment. In this study, we generated mice with macrophage-specific expression of the output clock gene E4BP4, which connects circadian rhythms downstream. When these mice were subjected to colitis using DSS, these mice were found to have less severe colitis than wild-type mice. Further investigation suggested that E4BP4 in macrophages may induce macrophages to polarize into anti-inflammatory macrophages and accelerate recovery from colitis.

Free Research Field

免疫学、血液学

Academic Significance and Societal Importance of the Research Achievements

今回、マクロファージでのE4BP4は、マクロファージを抗炎症マクロファージへと分極誘導させ、大腸炎の重症度を低下させることが分かった。
マクロファージを抗炎症へと導く転写因子はほとんど報告されていない上、疫学的にシフトワーカーなど不規則な生活スタイルと炎症性腸疾患など自己免疫疾患との関連が報告されている。今回の時計遺伝子E4BP4のマクロファージでの抗炎症作用は、こうした病態を解明する上で興味深い知見となった。