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Regulatory mechanism of IL-33 in atopic dermatitis

Research Project

Project/Area Number 20K08653
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53050:Dermatology-related
Research InstitutionKyushu University

Principal Investigator

Tsuji Gaku  九州大学, 大学病院, 准教授 (20423551)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywordsアトピー性皮膚炎 / IL-33 / IL-37 / 芳香族炭化水素受容体
Outline of Research at the Start

アトピー性皮膚炎の発症と痒みにおいて重要な働きをする表皮細胞におけるIL-33の産生機構について研究します。さらに、芳香族炭化水素受容体を活性化する物質によって、IL-33の産生が抑制されることを証明したいと考えています。その際に、OVOL1というアトピー性皮膚炎の疾患感受性遺伝子が重要な働きをするのではないか、と考えています。この研究結果をアトピー性皮膚炎の新しい治療法の開発に繋げていきたいと考えています。

Outline of Final Research Achievements

The pathogenesis of atopic dermatitis consists of skin barrier dysfunction, type 2 immune response, and pruritis. Keratinocyte-derived IL-33 is closely related to these factors. In this study, we investigated the mechanism of IL-33 production in human keratinocytes. In the first year, we found that the chemical sensor aryl hydrocarbon receptor regulates IL-33 production. In the second year, we found that IL-37, an anti-inflammatory cytokine, negatively regulates IL-33 expression. Finally, we showed that IL-37 was regulated by aryl hydrocarbon receptors and suggested a possibility that aryl hydrocarbon receptor regulates the pathogenesis of atopic dermatitis via the balance between IL-33 and IL-37.

Academic Significance and Societal Importance of the Research Achievements

本研究で用いたタピナロフという薬剤は、現在、アトピー性皮膚炎の新規薬剤としてPhase3試験が国内で施行中である。本研究によって、タピナロフがアトピー性皮膚炎に対してどのような機序で効果を発揮するのか、分子生物学的な機序が明らかとなった。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (5 results)

All 2022 2021 2020

All Journal Article (4 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (1 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] Natural Compounds Tapinarof and Galactomyces Ferment Filtrate Downregulate IL-33 Expression via the AHR/IL-37 Axis in Human Keratinocytes2022

    • Author(s)
      Tsuji Gaku、Hashimoto-Hachiya Akiko、Matsuda-Taniguchi Tomoyo、Takai-Yumine Ayako、Takemura Masaki、Yan Xianghong、Furue Masutaka、Nakahara Takeshi
    • Journal Title

      Frontiers in Immunology

      Volume: 13

    • DOI

      10.3389/fimmu.2022.745997

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Antidiabetic Agent Metformin Inhibits IL-23 Production in Murine Bone-Marrow-Derived Dendritic Cells2021

    • Author(s)
      Matsuda-Taniguchi Tomoyo、Takemura Masaki、Nakahara Takeshi、Hashimoto-Hachiya Akiko、Takai-Yumine Ayako、Furue Masutaka、Tsuji Gaku
    • Journal Title

      Journal of Clinical Medicine

      Volume: 10 Issue: 23 Pages: 5610-5610

    • DOI

      10.3390/jcm10235610

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Aryl Hydrocarbon Receptor Activation Downregulates IL-33 Expression in Keratinocytes via Ovo-Like 12020

    • Author(s)
      Tsuji Gaku、Hashimoto-Hachiya Akiko、Yen Vu Hai、Miake Sho、Takemura Masaki、Mitamura Yasutaka、Ito Takamichi、Murata Maho、Furue Masutaka、Nakahara Takeshi
    • Journal Title

      Journal of Clinical Medicine

      Volume: 9 Issue: 3 Pages: 891-891

    • DOI

      10.3390/jcm9030891

    • Related Report
      2020 Research-status Report
  • [Journal Article] IL-24 Negatively Regulates Keratinocyte Differentiation Induced by Tapinarof, an Aryl Hydrocarbon Receptor Modulator: Implication in the Treatment of Atopic Dermatitis2020

    • Author(s)
      Vu Yen Hai、Hashimoto-Hachiya Akiko、Takemura Masaki、Yumine Ayako、Mitamura Yasutaka、Nakahara Takeshi、Furue Masutaka、Tsuji Gaku
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 24 Pages: 9412-9412

    • DOI

      10.3390/ijms21249412

    • Related Report
      2020 Research-status Report
  • [Presentation] Mechanism and future prospects of IL-4 / 13 in the treatment of atopic dermatitis2021

    • Author(s)
      Gaku Tsuji
    • Organizer
      The 46 th Annual Meeting of The Japanese Society for Investigative Dermatology
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited

URL: 

Published: 2020-04-28   Modified: 2024-01-30  

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