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Hypomorphic CARD11 mutation developed inflammatory atopic disorders in mice

Research Project

Project/Area Number 19K17804
Research Category

Grant-in-Aid for Early-Career Scientists

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

Principal Investigator

Nomoto Yusuke  鹿児島大学, 鹿児島大学病院, 医員 (10781487)

Project Period (FY) 2019-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsCARD11 / atopic disorders / Treg / atopic dermatitis / Carma1 / TEM / Th2 / L815P / アトピー性皮膚炎 / Omenn症候群
Outline of Research at the Start

リンパ球の活性化や分化不全が背景となり、低IgM、高IgE、好酸球増多、アトピー性皮膚炎等を特徴とする難治性アトピー性疾患(Atopic dermatitis: AD)を引き起こすことが数多く報告されているが、その発症メカニズムは不明な点が多い。また、CARD11の遺伝子異常とAD発症との関連が示唆されている。我々が作成したCARD11の機能喪失型点変異(L815P)マウス(以下KIマウス)が、同症状を呈することを見出した。本研究では、このマウスを解析し、免疫不全を背景とするAD様炎症疾患の発生メカニズムの解明を目指す。

Outline of Final Research Achievements

T cells from diseased CARD11L815P mice produced higher IL-4 but not IFN-γ and IL-17A.Suggesting that T cells in KI mice were skewed to Th2 phenotype. Ratio of Tems/eTregs was Increased in diseased CARD11815P mice. WT bone marrow-derived cells including Tregs inhibited the development of dermatitis and suppressed the development of KI-derived Tems. We suggested that Treg deficiency is responsible for the disease development and KI-derived Tems might contain pathogenic T cells responsible for skin inflammation.

Academic Significance and Societal Importance of the Research Achievements

CARD11 KIマウスを用いた実験で、現段階でアトピー性皮膚炎を含む皮膚炎の原因の1つとして、Tregの関与が関わっている可能性を示唆した。また、最近の報告でアトピー性皮膚炎だけでなく、重症アトピー性皮膚炎様症状を示すOmenn症候群とCARD11の遺伝子異常との関連が示唆されており、そのような疾患に対しても今後研究が進むことで新薬の開発に役立つ可能性がある。

Report

(3 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • Research Products

    (5 results)

All 2020 2019

All Presentation (5 results)

  • [Presentation] CARD11機能喪失型点変異マウスにおけるアトピー性疾患の発症機構解析2020

    • Author(s)
      野元裕輔
    • Organizer
      第186回鹿児島地方会
    • Related Report
      2020 Annual Research Report
  • [Presentation] CARD11機能喪失型点変異マウスにおけるアトピー性疾患発症機構の解析2019

    • Author(s)
      野元裕輔、安川晋輔、古江増隆、原 博満、金蔵拓郎
    • Organizer
      第71回日本皮膚科学会西部支部学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Analysis of the onset mechanism of atopic disorders in mice with a loss-of-function CARD11 mutation.2019

    • Author(s)
      Nomoto Y, Yasukawa S, Furue M, Hara H, Kanekura T
    • Organizer
      The 44th Annual Meeting of the Japanese Society for Investigative Dermatology
    • Related Report
      2019 Research-status Report
  • [Presentation] Analysis of the onset mechanism of atopic disorders in mice with a loss-of-function CARD11 mutation.2019

    • Author(s)
      Nomoto Y, Yasukawa S, Furue M, Hara H, Kanekura T
    • Organizer
      第33回表皮細胞研究会
    • Related Report
      2019 Research-status Report
  • [Presentation] Hypomorphic CARD11 mutation developed inflammatory atopic disorders in mice.2019

    • Author(s)
      Nomoto Y, Yasukawa S, Lizasa E, Matsumoto S, Furue M, Kanekura T, Hara H
    • Organizer
      The 48th Annual Meeting of The Japanese Society for Immunology
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2022-01-27  

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