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Effects of bitter taste receptors expressed in CD4+ T cells and regulatory T cells on sublingual immunotherapy

Research Project

Project/Area Number 18K07190
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49070:Immunology-related
Research InstitutionTokyo Metropolitan Institute of Medical Science

Principal Investigator

HIROI Takachika  公益財団法人東京都医学総合研究所, 疾患制御研究分野, 室長 (80228824)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsアレルギー / スギ花粉症 / 舌下免疫療法 / 粘膜免疫 / 苦味受容体 / 花粉症 / 苦味レセプター / 作用機序
Outline of Final Research Achievements

This study found that the bitter taste receptor (TAS2R) plays an important role in the elucidation of the mechanism of response to sublingual immunotherapy expressed on antigen-specific helper T cells. TAS2R expressed on CD4+ T cells in the peripheral blood of patients with observed sublingual immunotherapy was observed to be predominantly expressed TAS2R43. Furthermore, when treatment was continued in patients who were not effective in the first year, it was observed that the expression of TAS2R43 increased year by year after 2 and 3 years. These findings were considered to be of great use in understanding the pathology of cedar hay fever in the future and developing effective treatment methods.

Academic Significance and Societal Importance of the Research Achievements

スギ花粉症に代表されるアレルギー疾患は、発症原因が明らかにされていない。またこの疾患は年々増加の一途を辿っており、既に国民の半数近くの罹患者が認められている。根本的治療法として免疫療法が推奨されているが、その作用メカニズムも明らかではない。本研究は、舌下免疫療法の作用機序の一端を解明した。この結果は、アレルギー免疫療法における今後の治療効率や薬剤開発の大きな助けになると思われる。さらにアレルギー疾患の発症機序の解明に有効である結果である。さらに、苦味受容体43を治療効果のバイオマーカーとすれば治療効果を表す具体的な指標になると思われた。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (22 results)

All 2021 2020 2019 2018 Other

All Journal Article (12 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 12 results,  Open Access: 11 results) Presentation (9 results) (of which Invited: 2 results) Remarks (1 results)

  • [Journal Article] L-type amino acid transporter 1 inhibitor suppresses murine Th2 cell-mediated bronchial hyperresponsiveness independently of eosinophil accumulation.2021

    • Author(s)
      Ito D, Miura K, Saeki M, Yamasaki N, Ogata S, Koyama T, Hiroi T, Mori A, Endou H, Hayashi K, Kaminuma O
    • Journal Title

      Asia Pac Allergy.

      Volume: 11

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Suppressive effect of dexamethasone on murine Th9 cell-mediated nasal eosinophilic inflammation.2021

    • Author(s)
      Koyama T, Miura K, Yamasaki N, Ogata S, Ito D, Saeki M, Hiroi T, Mori A, Kaminuma O
    • Journal Title

      Asia Pac Allergy.

      Volume: 11

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A new mechanism of bronchial hyperresponsiveness revealed by murine Th9 cell-transferred asthma model.2020

    • Author(s)
      Saeki M, Kaminuma O, Hiroi T.
    • Journal Title

      日本薬理学雑誌

      Volume: 155 Pages: 375-380

    • NAID

      130007933869

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] T cell-mediated nasal hyperresponsiveness in allergic rhinitis.2020

    • Author(s)
      Kaminuma O, Nishimura T, Saeki M, Mori A, Hiroi T.
    • Journal Title

      Biol Pharm Bull.

      Volume: 43 Pages: 36-40

    • NAID

      130007779207

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epicutaneous allergen administration without antigen delivery device induces local T cell response and alleviates food allergic enteropathy.2020

    • Author(s)
      Morinaga M, Nakajima-Adachi H, Hiraide E, Kitamura N, Kaminuma O, Hiroi T, Ohashi-Doi K, Hachimura S.
    • Journal Title

      Allergology International

      Volume: 69 Pages: 622-625

    • NAID

      130007926236

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ablation of IL-17A leads to severe colitis in IL-10-deficient mice: implications of myeloid-derived suppressor cells and NO production.2020

    • Author(s)
      Tachibana M, Watanabe N, Koda Y, Oya Y, Kaminuma O, Katayama K, Fan Z, Sakurai F, Kawabata K, Hiroi T and Mizuguchi H
    • Journal Title

      Int Immunol.

      Volume: 32 Issue: 3 Pages: 187-201

    • DOI

      10.1093/intimm/dxz076

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Development of Rice-Seed-Based Oral Allergy Vaccines Containing Hypoallergenic Japanese Cedar Pollen Allergen Derivatives for Immunotherapy.2019

    • Author(s)
      Takaiwa F, Yang L, Takagi H, Maruyama N, Wakasa Y, Ozawa K, Hiroi T.
    • Journal Title

      J Agric Food Chem.

      Volume: 67 Issue: 47 Pages: 13127-13138

    • DOI

      10.1021/acs.jafc.9b05421

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Mechanisms of allergen immunotherapy elucidated through integrated comparative analysis2019

    • Author(s)
      Kaminuma O, Gotoh M, Okubo K, Nakaya A, Hiroi T.
    • Journal Title

      Folia Pharmacologica Japonica

      Volume: 154 Issue: 1 Pages: 23-27

    • DOI

      10.1254/fpj.154.23

    • NAID

      130007678408

    • ISSN
      0015-5691, 1347-8397
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Potential mechanisms of T cell-mediated and eosinophil-independent bronchial hyperresponsiveness.2019

    • Author(s)
      Saeki M, Kaminuma O, Nishimura T, Kitamura N, Mori A, Hiroi T.
    • Journal Title

      Int J Mol Sci.

      Volume: 20 Issue: 12 Pages: 2980-2981

    • DOI

      10.3390/ijms20122980

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Thrombospondin 1-mediated suppression of mast cell degranulation is involved in the efficacy of sublingual immunotherapy2019

    • Author(s)
      Kaminuma O, Kitamura N, Gotoh M, Shindo M, Watanabe N, Saeki M, Nishimura T, Mori A, Nemoto S, Tatsumi H, Okubo K, Hiroi T.
    • Journal Title

      Allergology International

      Volume: 68 Issue: Supplement.1 Pages: S9-S10

    • DOI

      10.1016/j.alit.2019.03.007

    • NAID

      130007709743

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Involvement of taste receptoer in the effectiveness of subligual immunotherapy2019

    • Author(s)
      Gotoh Minoru、Kaminuma Osamu、Nakaya Akihiro、Katayama Kazufumi、Akihiroi Nakaya、Watanabe Nobumasa、Saeki Mayumi、Nishimura Tomoe、Kitamura Noriko、Okubo Kimihiro、Hiroi Takachika
    • Journal Title

      Allegology international

      Volume: 67 Pages: 421-424

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Serum interactions are implicated in the mechanism of action of sublingual immunotherapy for Japanese ceder pollinosis2018

    • Author(s)
      Kenichi Shimada、Minoru Gotoh、Kimihiro Okubo、Takachika Hiroi、Osamu Kaminuma、Akihiroi Nakaya
    • Journal Title

      J Nippon Med Sch

      Volume: 85 Pages: 250-258

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Calcineurin / NFATシグナルのダイバーシティを生む分子メカニズム.2020

    • Author(s)
      神沼修,北村紀子,宮武昌一郎,森晶夫,廣井隆親.
    • Organizer
      第93回日本生化学会大会.
    • Related Report
      2020 Research-status Report
  • [Presentation] 花粉症患者CD4陽性T細胞におけるカフェインの効果について.2020

    • Author(s)
      北村紀子,佐伯真弓,神沼修,廣井隆親,後藤穣.
    • Organizer
      第4回アレルギー学会関東地方会.
    • Related Report
      2020 Research-status Report
  • [Presentation] 経口免疫療法用デバイスとしての米蛋白顆粒の有用性.2019

    • Author(s)
      佐伯真弓、西村友枝、神沼 修、高木英典、森 晶夫、高岩文雄、廣井隆親.
    • Organizer
      アレルギー・好酸球研究会2019.
    • Related Report
      2019 Research-status Report
  • [Presentation] アレルゲン免疫療法の効果発現に関わる好塩基球およびマスト細胞関連メディエーター2019

    • Author(s)
      神沼 修、後藤 穣、中谷明弘、北村紀子、西村友枝、佐伯真弓、廣井隆親、森 晶夫、大久保公裕.
    • Organizer
      アレルギー・好酸球研究会2019.
    • Related Report
      2019 Research-status Report
  • [Presentation] アレルゲン発現米による制御性T細胞の誘導を介さない免疫寛容誘導.2019

    • Author(s)
      佐伯真弓、西村友枝、神沼 修、高木英典、森 晶夫、高岩文雄、廣井隆親.
    • Organizer
      第68回日本アレルギー学会学術大会.
    • Related Report
      2019 Research-status Report
  • [Presentation] Differential mechanisms of Th2- and Th9-mediated bronchial hyperresponsiveness in mice.2019

    • Author(s)
      Kaminuma O, Saeki M, Nishimura T, Kitamura N, Mori A, Hiroi T.
    • Organizer
      第68回日本アレルギー学会学術大会.
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 舌下免疫療法における味覚受容体を介した奏功メカニズム.2019

    • Author(s)
      佐伯真弓、後藤 穣、大久保公裕、中谷明弘、北村紀子、西村友枝、神沼 修、廣井隆親.
    • Organizer
      第1回日本アレルギー学会関東地方会.
    • Related Report
      2019 Research-status Report
  • [Presentation] 花粉症舌下免疫療法の効果発現機序の探索.2019

    • Author(s)
      北村紀子、後藤 穣、湯田厚司、佐伯真弓、神沼 修、廣井隆親.
    • Organizer
      第1回日本アレルギー学会関東地方会.
    • Related Report
      2019 Research-status Report
  • [Presentation] スギ花粉症舌下免疫療法の個別化医療を目指した基礎研究2018

    • Author(s)
      廣井隆親
    • Organizer
      東京都福祉保健医療学会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Remarks] 東京都医学総合研究所における花粉症研究

    • URL

      http://www.igakuken.or.jp/

    • Related Report
      2019 Research-status Report 2018 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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