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Induction of tolerance by concomitant use of kakkonto with oral immunotherapy and exploration of candidate blood marker that enable evaluation of the effects of treatments for food allergy

Research Project

Project/Area Number 19K07908
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52010:General internal medicine-related
Research InstitutionUniversity of Toyama

Principal Investigator

Yamamoto Takeshi  富山大学, 学術研究部薬学・和漢系, 助教 (70316181)

Project Period (FY) 2019-04-01 – 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 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords食物アレルギー / 経口免疫療法 / 腸管粘膜免疫系 / 漢方薬 / 腸管粘膜免疫 / 葛根湯 / 制御性T細胞 / レチノイン酸
Outline of Research at the Start

未だ治療法が確立していない食物アレルギーを安全で治療効率が良く根本的に治癒するため、経口免疫療法(OIT)に葛根湯を併用する治療法を検討し、葛根湯の併用が脱感作誘導率を有意に上げることを明らかにしている。そこで本研究では、葛根湯併用OITによる耐性獲得の誘導を検討するとともに、詳細な治療機序を解明する。また、病態モデルの血液分析から、臨床応用可能な耐性獲得の誘導を評価する新たな血液バイオマーカーを見出すことを目的とする。

Outline of Final Research Achievements

We investigated the treatment of food allergy using an oral immunotherapy model and a sustained unresponsiveness model, and clarified that the concomitant use of kakkonto with oral immunotherapy increased the rate of desensitization and the rate of remission maintenance. Furthermore, we clarified that the induction of regulatory T cells and the suppression of mucosal mast cell activity are committed to the mechanisms underlying the treatment of food allergy. We also identified several active components associated with kakkonto. Therefore, these findings indicated that the effectiveness of oral immunotherapy in combination with Kampo medicine such as kakkonto.

Academic Significance and Societal Importance of the Research Achievements

いまだ治療法が確立していない食物アレルギーに対して、臨床に則した病態モデルを用いて治療効果の検討を行い、臨床研究では利用できない腸管を用いた腸管粘膜免疫系での脱感作誘導や耐性獲得の治療機序の検討行い、葛根湯併用による耐性獲得率向上とその機序を明らかにした。また、メタボローム解析により治療効果を示す血液バイオマーカーの探索も行った。漢方薬は既に臨床現場で使われているため、漢方薬リポジショニングとして臨床に応用し易く、独自性のある新規治療法として実現できる可能性が高く、既存の経口免疫寛容の主な問題点の改善につながる食物アレルギーの治療として社会的ニーズに答えた波及効果の高い研究になったと考える。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (23 results)

All 2023 2022 2021 2020 2019 Other

All Int'l Joint Research (1 results) Journal Article (10 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 10 results,  Open Access: 9 results) Presentation (12 results) (of which Int'l Joint Research: 4 results)

  • [Int'l Joint Research] Shanghai University of TCM(中国)

    • Related Report
      2020 Research-status Report
  • [Journal Article] Allergic inflammation disrupts epithelial electrogenic electrolyte transport through cholinergic regulation in the mouse colon2023

    • Author(s)
      Yamamoto Takeshi, Katsuki Yosuke, Kanauchi Yuya, Hayashi Shusaku, Kadowaki Makoto
    • Journal Title

      Biomedical Research

      Volume: 44 Issue: 1 Pages: 31-40

    • DOI

      10.2220/biomedres.44.31

    • ISSN
      0388-6107, 1880-313X
    • Year and Date
      2023-01-25
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neuro-immune crosstalk and food allergy: Focus on enteric neurons and mucosal mast cells2022

    • Author(s)
      Kadowaki Makoto, Yamamoto Takeshi, Hayashi Shusaku
    • Journal Title

      Allergology International

      Volume: 71 Issue: 3 Pages: 278-287

    • DOI

      10.1016/j.alit.2022.03.004

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cholinergic anti-inflammatory pathway ameliorates murine experimental Th2-type colitis by suppressing the migration of plasmacytoid dendritic cells2022

    • Author(s)
      Kanauchi Yuya、Yamamoto Takeshi、Yoshida Minako、Zhang Yue、Lee Jaemin、Hayashi Shusaku、Kadowaki Makoto
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 54-54

    • DOI

      10.1038/s41598-021-04154-2

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Suppression of plasmacytoid dendritic cell migration to colonic isolated lymphoid follicles abrogates the development of colitis2021

    • Author(s)
      Zhang Yue、Yamamoto Takeshi、Hayashi Shusaku、Kadowaki Makoto
    • Journal Title

      Biomedicine & Pharmacotherapy

      Volume: 141 Pages: 111881-111881

    • DOI

      10.1016/j.biopha.2021.111881

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Pathophysiological Roles of Neuro-Immune Interactions between Enteric Neurons and Mucosal Mast Cells in the Gut of Food Allergy Mice2021

    • Author(s)
      Yashiro Tomoe、Ogata Hanako、Zaidi Syed Faisal、Lee Jaemin、Hayashi Shusaku、Yamamoto Takeshi、Kadowaki Makoto
    • Journal Title

      Cells

      Volume: 10 Issue: 7 Pages: 1586-1586

    • DOI

      10.3390/cells10071586

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of key pathways and gene expression in the activation of mast cells via calcium flux using bioinformatics analysis2021

    • Author(s)
      Wang X, Yamamoto T, Kadowaki M, Yang Y
    • Journal Title

      BIOCELL

      Volume: 45 Issue: 2 Pages: 395-415

    • DOI

      10.32604/biocell.2021.012280

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Isoflavones Suppress Cyp26b1 Expression in the Murine Colonic Lamina Propria2020

    • Author(s)
      Yamamoto Takeshi、Nagata Yuka、Hayashi Shusaku、Kadowaki Makoto
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 43 Issue: 12 Pages: 1945-1949

    • DOI

      10.1248/bpb.b20-00355

    • NAID

      130007948731

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2020-12-01
    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ginger Increases ALDH1A1 Expression and Enhances Retinoic Acid Signaling in a Human Colonic Epithelial Cell Line2020

    • Author(s)
      Nagata Y, Yamamoto T, Kadowaki M.
    • Journal Title

      Journal of Nutritional Science and Vitaminology

      Volume: 66 Issue: 5 Pages: 462-467

    • DOI

      10.3177/jnsv.66.462

    • NAID

      130007932347

    • ISSN
      0301-4800, 1881-7742
    • Year and Date
      2020-10-31
    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Therapeutic Benefit in Allergic Dermatitis Derived from the Inhibitory Effect of Byakkokaninjinto on the Migration of Plasmacytoid Dendritic Cells2020

    • Author(s)
      Yamamoto Takeshi、Zhang Yue、Kigasawa Ai、Hayashi Shusaku、Kadowaki Makoto
    • Journal Title

      Evidence-Based Complementary and Alternative Medicine

      Volume: 2020 Issue: 1 Pages: 1-10

    • DOI

      10.1155/2020/9532475

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The isoflavone puerarin induces Foxp3+ regulatory T cells by augmenting retinoic acid production, thereby inducing mucosal immune tolerance in a murine food allergy model2019

    • Author(s)
      Yamamoto Takeshi、Matsunami Emi、Komori Koji、Hayashi Shusaku、Kadowaki Makoto
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 516 Issue: 3 Pages: 626-631

    • DOI

      10.1016/j.bbrc.2019.06.051

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] GPR41-positive enteric sensory neurons are in close proximity to intestinal macrophages in the colonic mucosa of murine colitis model.2022

    • Author(s)
      Hayashi Shusaku, Hertati Ai, Yamamoto Takeshi, Kadowaki Makoto.
    • Organizer
      Cell Symposia: The Neuro-Immune Axis; Lisbon.
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Neurogenesis and neurodegeneration in enteric neurons of DSS colitis mouse colon.2022

    • Author(s)
      Miyata Kana, Ogata Hanako, Yamamoto Takeshi, Hayashi Shusaku, Kadowaki Makoto.
    • Organizer
      Cell Symposia: The Neuro-Immune Axis; Lisbon.
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 病態モデルマウスを用いたAhRアゴニストによる食物アレルギーの治療効果の検討2022

    • Author(s)
      山本武,後藤由佳,門脇真.
    • Organizer
      第39回和漢医薬学会学術大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 芳香族炭化水素受容体活性化の食物アレルギーへの効果と制御性T細胞の誘導の病態マウスを用いた検討.2022

    • Author(s)
      山本武,後藤由佳,門脇真
    • Organizer
      第71回日本アレルギー学会学術大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 葛根湯併用経口免疫療法による食物アレルギー治療の粘膜型マスト細胞脱顆粒抑制作用とその機序の検討.2021

    • Author(s)
      山本 武, 後藤由佳, 門脇 真.
    • Organizer
      第38回和漢医薬学会学術大会
    • Related Report
      2021 Research-status Report
  • [Presentation] 食物アレルギー病態マウスを用いた長期葛根湯併用による経口免疫療法の寛解維持効果向上の検討.2021

    • Author(s)
      山本 武, 後藤由佳, 門脇 真.
    • Organizer
      第70回日本アレルギー学会学術大会
    • Related Report
      2021 Research-status Report
  • [Presentation] An evaluation of the effects of Kakkonto in combination with dietary advice in children with food allergies through a non-randomized controlled trial.2020

    • Author(s)
      Kato T., Ito Y., Yamamoto T., Shimizu M., Itazawa T., Adachi Y., Kadowaki M., Adachi Y.
    • Organizer
      JSA/WAO Joint Congress 2020
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] 葛根湯併用経口免疫療法による食物アレルギー疾患の寛解維持誘導について病態マウスを用いた検討.2020

    • Author(s)
      山本 武,宋 夢テイ,後藤由佳,門脇 真.
    • Organizer
      第37回和漢医薬学会学術大会
    • Related Report
      2020 Research-status Report
  • [Presentation] 食物アレルギー病態マウスを用いた葛根湯と経口免疫療法の併用療法による寛解維持効果の検討.2020

    • Author(s)
      山本 武,宋 夢テイ,後藤由佳,門脇 真.
    • Organizer
      JSA/WAO Joint Congress 2020 (第69回日本アレルギー学会学術大会)
    • Related Report
      2020 Research-status Report
  • [Presentation] 葛根湯と経口免疫療法の併用療法による粘膜型マスト細胞の活性化抑制を介した脱感作誘導率の向上2019

    • Author(s)
      山本 武, 林美智慧, 長田夕佳, 門脇 真
    • Organizer
      第68回日本アレルギー学会学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] AhR agonist combined with oral immunotherapy can alleviate food allergy by induction of CD4+Foxp3+ regulatory T cells in the colon of food allergy model mice.2019

    • Author(s)
      Yamamoto T., Gou Q., Kadowaki M.
    • Organizer
      19th International Congress of Mucosal Immunology
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Induction of desensitization by combined therapy with oral immunotherapy and kakkonto in food allergy.2019

    • Author(s)
      Song M., Yamamoto T., Nagata Y., Kadowaki M.
    • Organizer
      第36回 和漢医薬学会学術大会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2024-01-30  

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