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A novel treatment of allergy by mucosal barrier enhancement through selective IgA class switching

Research Project

Project/Area Number 18K19559
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 54:Internal medicine of the bio-information integration and related fields
Research InstitutionThe University of Tokyo

Principal Investigator

Shinkura Reiko  東京大学, 定量生命科学研究所, 教授 (50362471)

Co-Investigator(Kenkyū-buntansha) 磯谷 綾子  奈良先端科学技術大学院大学, 先端科学技術研究科, 准教授 (20444523)
孫 安生  東京大学, 定量生命科学研究所, 助教 (30447924)
森田 直樹  東京大学, 定量生命科学研究所, 助教 (80845107)
Project Period (FY) 2018-06-29 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2018: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Keywordsアレルギー / クラススイッチ / IgA / IgA抗体 / 抗体
Outline of Final Research Achievements

Allergic diseases are associated with crosslinking of the high-affinity Fc receptor for immunoglobulin E (IgE) on mast cells or basophils. Therefore, most of the current treatments seek to inhibit IgE responses. However, these treatments are still not curative because they do not prevent the allergen invasion into our body. We performed the chemical compound screenings, and identified three compounds that specifically induced IgA production in whole spleen cell culture. These compounds were protein kinase C (PKC) activators and well-known carcinogenic chemicals. Therefore, we searched non-carcinogenic PKC activators and identified Bryostatin1 as a non-carcinogenic PKC activator. We confirmed that Bryostatin1 also induced IgA production but not IgE production in whole spleen cell culture and also that Bryostatin1 inhibited the IgE response in mouse allergic model.

Academic Significance and Societal Importance of the Research Achievements

私たちはアレルゲンが体内に侵入することがその根本原因ではないかと考えている。つまり、アレルギーの根本治療はアレルゲンの体内侵入を減らすことであると考える。一連の免疫反応の流れをどこかで遮断するのではなく、アウトプットを横道にそらし(IgAへの選択的クラススイッチ誘導)、その結果として粘膜防御を強固にすることでアレルゲンの侵入を減らし、一連の反応のおおもとであるTh2優位な状況をも是正しようという試みであり、今までのアレルギー治療にはなかった概念である。選択的IgAクラススイッチ誘導により、アレルゲンの侵入を減らすことから対症療法ではなくアレルギーの根本的治療となりうる。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (4 results)

All 2018 Other

All Presentation (2 results) Remarks (2 results)

  • [Presentation] 1.The selective induction of IgA production by PKC activators.2018

    • Author(s)
      Aoi Son, Hitomi, Sakatani, Reiko Shinkura.
    • Organizer
      The 47th Annual Meeting of the Japanese Society for Immunology
    • Related Report
      2018 Research-status Report
  • [Presentation] The specific induction of IgA production by PKC activators.2018

    • Author(s)
      Hitomi Sakatani, Aoi Son, Reiko Shinkura.
    • Organizer
      The 41th Annual Meeting of the Molecular Biology Society of Japan
    • Related Report
      2018 Research-status Report
  • [Remarks]

    • URL

      http://www.iam.u-tokyo.ac.jp/shinkuralab/

    • Related Report
      2019 Annual Research Report
  • [Remarks] 東京大学定量生命科学研究所 免疫・感染制御研究分野

    • URL

      http://www.iam.u-tokyo.ac.jp/shinkuralab/

    • Related Report
      2018 Research-status Report

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Published: 2018-07-25   Modified: 2021-02-19  

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