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

Research Project

Project/Area Number 22K16353
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 54020:Connective tissue disease and allergy-related
Research InstitutionChiba 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
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2023: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2022: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords気道上皮細胞 / エピジェネティクス
Outline of Research at the Start

気管支喘息と気道感染症の相互増悪機構は喘息の難治化に寄与することが推測され、古くから多くの研究が行われている。近年、喘息患者由来の気道上皮細胞は、健常人由来の気道上皮細胞に比して、ウイルス感染応答が遅延することが示された。他方、皮膚では上皮幹細胞がエピジェネティック変化を介して過去の炎症を記憶し、その後の反応性を変化させることが報告された。本研究では、「アレルギー性炎症による気道上皮細胞のエピジェネティック変化を介した炎症記憶がその後の気道炎症の強度に影響する。」との仮説のもと、気道上皮細胞の炎症記憶への介入による新規気道炎症制御法の開発基盤を構築する。

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.

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。

Report

(3 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • Research Products

    (5 results)

All 2023

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (1 results)

  • [Journal Article] TAp63, a methotrexate target in CD4+ T cells, suppresses Foxp3 expression and exacerbates autoimmune arthritis2023

    • Author(s)
      Suga Kensuke、Suto Akira、Tanaka Shigeru、Sugawara Yutaka、Kageyama Takahiro、Ishikawa Junichi、Sanayama Yoshie、Ikeda Kei、Furuta Shunsuke、Kagami Shin-Ichiro、Iwata Arifumi、Hirose Koichi、Suzuki Kotaro、Ohara Osamu、Nakajima Hiroshi
    • Journal Title

      JCI Insight

      Volume: 8 Issue: 10

    • DOI

      10.1172/jci.insight.164778

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Single-cell RNA sequencing of peripheral blood mononuclear cells from Kimura disease patient successfully treated with dupilumab2023

    • Author(s)
      Suga Kensuke、Kiuchi Masahiro、Kageyama Takahiro、Kokubo Kota、Tanaka Shigeru、Iwata Arifumi、Suzuki Kotaro、Hirahara Kiyoshi、Nakajima Hiroshi
    • Journal Title

      Allergology International

      Volume: 72 Issue: 4 Pages: 610-613

    • DOI

      10.1016/j.alit.2023.06.002

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] IL-21 is required for the maintenance and pathogenesis of murine Vγ4+ IL-17-producing γδT cells2023

    • Author(s)
      Ishikawa Junichi、Suto Akira、Abe Kazuya、Hayashi Yuki、Suga Kensuke、Tanaka Shigeru、Kageyama Takahiro、Iwata Arifumi、Suzuki Kazumasa、Suzuki Kotaro、Nakajima Hiroshi
    • Journal Title

      Frontiers in Immunology

      Volume: 14 Pages: 1211620-1211620

    • DOI

      10.3389/fimmu.2023.1211620

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epithelial cell-derived cytokine TSLP modulates metabolic program of regulatory T cells by enhancing fatty acid uptake to suppress the intestinal inflammation2023

    • Author(s)
      Kasuya T., Tanaka S., Etori K., Shoda J., Hattori K., Endo Y., Kitajima M., Kageyama T., Iwamoto T., Yokota M., Iwata A., Suto A., Suzuki K., Suzuki H., Ziegler SF., and Nakajima H
    • Journal Title

      Sci. Rep.

      Volume: 13 Issue: 1 Pages: 1653-1653

    • DOI

      10.1038/s41598-023-28987-1

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] デュピルマブが奏効した木村病患者の治療前後における末梢血単核球のシングルセル(sc)RNA-seq解析2023

    • Author(s)
      須賀謙介、影山貴弘、田中繁、岩田有史、鈴木浩太郎、中島裕史
    • Organizer
      第72回日本アレルギー学会学術大会
    • Related Report
      2023 Annual Research Report

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Published: 2022-04-19   Modified: 2025-01-30  

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