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Development of new strategies to enhance the efficacy of sublingual immunotherapy by targeting oral dendritic cells

Research Project

Project/Area Number 21K09837
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57020:Oral pathobiological science-related
Research InstitutionTohoku University

Principal Investigator

Tanaka Yukinori  東北大学, 大学病院, 講師 (60637958)

Co-Investigator(Kenkyū-buntansha) 水田 健太郎  東北大学, 歯学研究科, 教授 (40455796)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2023: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords舌下免疫療法 / 樹状細胞 / 制御性T細胞 / 免疫寛容 / 制御性 T 細胞
Outline of Research at the Start

舌下免疫療法は抗原(アレルゲン)を舌下粘膜から吸収させ、体質の改善を図る簡易かつ有効なアレルギー治療法であり、花粉症などアレルギー性鼻炎の一般的な治療法として普及している。しかし、現行のプロトコールでは数年に渡り毎日の舌下投与が必要であるため、患者への負担が大きい。そのため、免疫療法の効果を増強させて治療期間の短縮を図る手法の開発が切望されている。舌下免疫療法によりアレルギーが抑えられる主要なメカニズムとして、制御性 T 細胞の誘導が挙げられる。本研究では、口腔樹状細胞による制御性T細胞誘導を強化する免疫賦活剤として各種ビタミン誘導体を用いて、舌下免疫療法の効果を増強させる方法を開発する。

Outline of Final Research Achievements

This study aimed to develop a method to enhance the efficacy of sublingual immunotherapy using a mouse allergy model with ovalbumin as a model antigen. Toward this goal, retinoic acid, niacin, butyrate, and rapamycin were examined as candidate adjuvants that are able to increase the induction efficiency of regulatory T cells, which are an important cellular mediator of sublingual immunotherapy. The administration of rapamycin increased the induction efficiency of regulatory T cells by sublingual immunotherapy. It took 10 weeks for sublingual immunotherapy to exert its therapeutic effect for established food allergy. Therefore, above candidate adjuvants were combined with sublingual immunotherapy to shorten the treatment period to 3 weeks. However, favorable results were not obtained.

Academic Significance and Societal Importance of the Research Achievements

舌下免疫療法は抗原(アレルゲン)を舌下粘膜から吸収させ、体質の改善を図る根本的なアレルギー治療法である。花粉症などアレルギー性鼻炎の治療法として普及しているが、現行のプロトコールでは数年に渡り毎日の舌下投与が必要である。舌下免疫療法の治療効果を増強する免疫賦活剤を発見できれば、治療期間の短縮や、食物アレルギーなど適応症の拡大につながる可能性があり、社会的意義は大きい。ラパマイシンは舌下免疫療法による食物アレルギー治療モデルでの有効性は示されなかったが、制御性 T 細胞誘導効率は明確に向上させたため、有望な候補物質として今後さらなる研究が期待される。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (11 results)

All 2023 2022 2021 Other

All Journal Article (8 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 8 results,  Open Access: 4 results) Presentation (2 results) Remarks (1 results)

  • [Journal Article] Lipopolysaccharide Priming Exacerbates Anaphylatoxin C5a-Induced Anaphylaxis in Mice2023

    • Author(s)
      Yasuda Makoto、Tanaka Yukinori、Bando Kanan、Sugawara Shunji、Mizuta Kentaro
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 46 Issue: 3 Pages: 432-439

    • DOI

      10.1248/bpb.b22-00766

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2023-03-01
    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Skin‐derived TSLP stimulates skin migratory dendritic cells to promote the expansion of regulatory T cells2023

    • Author(s)
      Tanaka Yukinori、Yokoyama Yuichi、Kambayashi Taku
    • Journal Title

      European Journal of Immunology

      Volume: 53 Issue: 10

    • DOI

      10.1002/eji.202350390

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Diacylglycerol kinase zeta deficiency attenuates papain-induced type 2 airway inflammation2023

    • Author(s)
      Singh Brenal K.、Yokoyama Yuichi、Tanaka Yukinori、Laczko Dorottya、Deshpande Deepak A.、Kambayashi Taku
    • Journal Title

      Cellular Immunology

      Volume: 393-394 Pages: 104780-104780

    • DOI

      10.1016/j.cellimm.2023.104780

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] IL-33 induces histidine decarboxylase, especially in c-kit+ cells and mast cells, and roles of histamine include negative regulation of IL-33-induced eosinophilia2023

    • Author(s)
      Bando Kanan、Tanaka Yukinori、Winias Saka、Sugawara Shunji、Mizoguchi Itaru、Endo Yasuo
    • Journal Title

      Inflammation Research

      Volume: 72 Issue: 3 Pages: 651-667

    • DOI

      10.1007/s00011-023-01699-y

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Histamine acts via H4-receptor stimulation to cause augmented inflammation when lipopolysaccharide is co-administered with a nitrogen-containing bisphosphonate2022

    • Author(s)
      Bando Kanan、Tanaka Yukinori、Takahashi Tetsu、Sugawara Shunji、Mizoguchi Itaru、Endo Yasuo
    • Journal Title

      Inflammation Research

      Volume: 71 Issue: 12 Pages: 1603-1617

    • DOI

      10.1007/s00011-022-01650-7

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Differential expression of CD11c defines two types of tissue-resident macrophages with different origins in steady-state salivary glands2022

    • Author(s)
      Lu Lu, Toshinobu Kuroishi, Yukinori Tanaka, Mutsumi Furukawa, Tomonori Nochi, Shunji Sugawara
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 931-931

    • DOI

      10.1038/s41598-022-04941-5

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Salt-Sensitive Hypertension Induces Osteoclastogenesis and Bone Resorption via Upregulation of Angiotensin II Type 1 Receptor Expression in Osteoblasts2022

    • Author(s)
      Adya Pramusita, Hideki Kitaura, Fumitoshi Ohori, Takahiro Noguchi, Aseel Marahleh, Yasuhiko Nara, Ria Kinjo, Jinghan Ma, Kayoko Kanou, Yukinori Tanaka and Itaru Mizoguchi
    • Journal Title

      Frontiers in Cell and Developmental Biology

      Volume: 10 Pages: 816764-816764

    • DOI

      10.3389/fcell.2022.816764

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nitrogen-containing bisphosphonates and lipopolysaccharide mutually augment inflammation via adenosine triphosphate (ATP)-mediated and interleukin 1β (IL-1β)-mediated production of neutrophil extracellular traps (NETs)2021

    • Author(s)
      Kanan Bando, Toshinobu Kuroishi, Hiroyuki Tada, Takefumi Oizumi, Yukinori Tanaka, Tetsu Takahashi, Itaru Mizoguchi, Shunji Sugawara, Yasuo Endo
    • Journal Title

      Journal of Bone and Mineral Research

      Volume: 36 Issue: 9 Pages: 1866-1878

    • DOI

      10.1002/jbmr.4384

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Dynamics of regulatory T cells in sublingual immunotherapy2023

    • Author(s)
      Saka Winias, Toshinobu Kuroishi, Shunji Sugawara, Yukinori Tanaka
    • Organizer
      第65回歯科基礎医学会学術大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] TSLPによる制御性T細胞拡大機構2023

    • Author(s)
      田中志典、水田健太郎
    • Organizer
      第51回日本歯科麻酔学会総会・学術集会
    • Related Report
      2023 Annual Research Report
  • [Remarks] 東北大学大学院歯学研究科 歯科口腔麻酔学分野

    • URL

      http://www.anes.dent.tohoku.ac.jp/index.html

    • Related Report
      2023 Annual Research Report

URL: 

Published: 2021-04-28   Modified: 2025-01-30  

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