Establishment of a novel method to control airway inflammation by intervening in the inflammatory memory of airway epithelial cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K16353
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Chiba University
• Principal Investigator: Kageyama Takahiro 千葉大学, 医学部附属病院, 特任助教 (40894267)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 気道上皮細胞

Outline of Final Research Achievements

After induction of chronic allergic airway inflammation in wild type mice, airway epithelial cells were isolated and subjected to single cell ATAC and RNA analysis. Open chromatin regions were induced in some cell populations after allergic inflammation, although RNA expression was not changed. I analyzed genes associated with the regions where inflammatory memory was thought to have been induced. The open chromatin regions induced in airway epithelial cells were shown to be enriched with genes related to cell dynamics and responsiveness to stimuli. I am currently analyzing the mechanism of induction of inflammatory memory and its function, and plan to conduct further experiments that will lead to a novel method of controlling airway inflammation.

Free Research Field

アレルギー

Academic Significance and Societal Importance of the Research Achievements

気管支喘息の治療は、各種抗体療法の登場などにより、長期管理薬の選択肢が増えた。しかし感染などを契機とした喘息の急性増悪は今も多く経験され、新たな機構を標的とした治療法の開発が必要である。近年、上皮細胞などの非免疫系細胞に免疫記憶が誘導されることが報告されたが、アレルギー性炎症に起因して非免疫細胞に免疫記憶が誘導されるのか、またその意義の詳細は不明であった。本研究の成果によって、アレルギー性気道炎症によって、気道上皮細胞にエピジェネティック炎症記憶が誘導されることが明らかとなった。今後、この誘導機構、機能をさらに解析することで、新たな治療法の開発に繋がるものと考える。