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Basic research on novel therapeutic strategies for metal allergy with oral tolerance

Research Project

Project/Area Number 19K10371
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57060:Surgical dentistry-related
Research InstitutionThe University of Tokyo (2020-2022)
Tsurumi University (2019)

Principal Investigator

KUMAGAI Kenichi  東京大学, 医学部附属病院, 助教 (10518129)

Co-Investigator(Kenkyū-buntansha) 濱田 良樹  鶴見大学, 歯学部, 教授 (70247336)
鈴木 隆二  独立行政法人国立病院機構(相模原病院臨床研究センター), 臨床免疫研究室, 室長 (70373470)
重松 宏昭  鶴見大学, 歯学部, 非常勤講師 (80737198)
Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords金属アレルギー / T細胞受容体 / 交差反応 / 経口免疫寛容
Outline of Research at the Start

本研究では世界に先駆けて口腔内での金属アレルギー動物モデルを確立し, 口腔内の金属アレルギーに関わるT細胞を中心とした免疫動態および口腔内の菌叢変化を明らかにしていく. また, 経口免疫寛容を誘導することで口腔粘膜における金属-細菌叢-生体防御系の関連性の観点から免疫応答制御機構を解明し, 金属アレルギーに関する新規診断・治療体系の礎となることを目的とする.

Outline of Final Research Achievements

In this study, we established the first animal model of metal allergy in the oral cavity, and clarified the immunokinetics and changes in oral microflora centered on T cells involved in metal allergy in the oral cavity. In addition, we conducted research with the aim of elucidating the immune response control mechanism from the viewpoint of the relationship between metal-bacterial flora-biological defense system in the oral mucosa by inducing oral immune tolerance, and to become the foundation of a new diagnostic and therapeutic system for metal allergy. In this study, we prepared allergy model mice using Pd, Cr, and Ni metals in the oral mucosa. Specific T cells involved in the development of oral metal allergy were identified, and cross-reactivity was also verified, and conference presentations and papers were presented.

Academic Significance and Societal Importance of the Research Achievements

口腔内での金属アレルギー動物モデルを作製したことで, 金属イオンが耳介部皮膚より経皮的に感作され,口腔内の金属からの溶出された金属イオンと生体内でアレルギー反応を示すことが明らかとなった. さらに口腔内の金属アレルギーには金属交差性も存在しており, とくに自然リンパ球および金属特異的T 細胞が病因・病態に深く関与している事が示唆された.

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

    (10 results)

All 2023 2022 2021 2020 2019

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (5 results) Book (1 results)

  • [Journal Article] Cross-Reactivity of Intraoral Allergic Contact Mucositis in the Nickel-Sensitized Ear Model of Metal Allergy2023

    • Author(s)
      Matsubara Ryota、Kumagai Kenichi、Nasu Keisuke、Yoshizawa Takamasa、Kitaura Kazutaka、Suzuki Motoaki、Hamada Yoshiki、Suzuki Ryuji
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 24 Issue: 4 Pages: 3965-3965

    • DOI

      10.3390/ijms24043965

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Type IVb Hypersensitivity Reaction in the Novel Murine Model of Palladium Induced Intraoral Allergic Contact Mucositis2023

    • Author(s)
      Nasu Keisuke、Kumagai Kenichi、Yoshizawa Takamasa、Kitaura Kazutaka、Matsubara Ryota、Suzuki Motoaki、Suzuki Ryuji、Hamada Yoshiki
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 24 Issue: 4 Pages: 3137-3137

    • DOI

      10.3390/ijms24043137

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Characterization of Metal-Specific T-Cells in Inflamed Oral Mucosa in a Novel Murine Model of Chromium-Induced Allergic Contact Dermatitis2023

    • Author(s)
      Yoshizawa Takamasa、Kumagai Kenichi、Matsubara Ryota、Nasu Keisuke、Kitaura Kazutaka、Suzuki Motoaki、Hamada Yoshiki、Suzuki Ryuji
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 24 Issue: 3 Pages: 2807-2807

    • DOI

      10.3390/ijms24032807

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cross-Reactivity of Palladium in a Murine Model of Metal-induced Allergic Contact Dermatitis2020

    • Author(s)
      Shigematsu Hiroaki、Kumagai Kenichi、Suzuki Motoaki、Eguchi Takanori、Matsubara Ryota、Nakasone Yasunari、Nasu Keisuke、Yoshizawa Takamasa、Ichikawa Haruno、Mori Takahiro、Hamada Yoshiki、Suzuki Ryuji
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 11 Pages: 4061-4061

    • DOI

      10.3390/ijms21114061

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 口腔内クロム誘発型金属アレルギーモデルマウスの確立と病態解明2022

    • Author(s)
      吉澤孝昌 , 熊谷賢一,那須啓佑,松原陵太, 重松宏昭, 北條秀樹, 鈴木隆二, 濱田良樹
    • Organizer
      第32回日本口腔内科学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 口腔粘膜に局在するパラジウムアレルギーにおける免疫応答の解明2022

    • Author(s)
      那須啓佑, 熊谷賢一,吉澤孝昌,松原陵太, 重松宏昭, 北條秀樹, 鈴木隆二, 濱田良樹
    • Organizer
      第69回日本口腔科学会 中国・四国地方部会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 自然リンパ球を介したチタンアレルギー免疫応答の解明2021

    • Author(s)
      熊谷賢一, 松原陵太, 仲宗根康成, 那須啓佑, 吉澤孝昌, 江口貴紀, 森隆弘, 鈴木隆二, 濱田良樹
    • Organizer
      第66回公益社団法人 日本口腔外科学会総会・学術大会
    • Related Report
      2021 Research-status Report
  • [Presentation] パラジウムアレルギー交差反応マウスモデルにおけるT 細胞免疫応答の解明について2021

    • Author(s)
      重松宏昭, 熊谷賢一,江口貴紀,松原陵太,仲宗根康成,那須啓佑,吉澤孝昌,馬杉亮彦,鈴木隆二,濱田良樹
    • Organizer
      第66回公益社団法人 日本口腔外科学会総会・学術大会
    • Related Report
      2021 Research-status Report
  • [Presentation] 異種金属間における口腔粘膜金属アレルギー交叉反応の免疫学的解析2019

    • Author(s)
      松原 陵太, 熊谷 賢一, 仲宗根 康成, 江口 貴紀, 重松 宏昭, 北條 秀樹, 吉澤 孝昌, 今村 栄作, 鈴木 隆二, 濱田 良樹
    • Organizer
      第64回公益社団法人 日本口腔外科学会総会・学術大会
    • Related Report
      2019 Research-status Report
  • [Book] 金属アレルギー発症モデルマウスによる病態解明と新規診断・治療法への可能性2021

    • Author(s)
      熊谷 賢一, 松原 陵太, 濱田 良樹, 鈴木 隆二
    • Total Pages
      5
    • Publisher
      アレルギーの臨床
    • Related Report
      2021 Research-status Report

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

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