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Mechanisms underlying the development of hyperresponsiveness commonly induced by T cell subsets in allergic diseases

Research Project

Project/Area Number 18K19561
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 InstitutionHiroshima University (2019-2020)
University of Yamanashi (2018)

Principal Investigator

Kaminuma Osamu  広島大学, 原爆放射線医科学研究所, 教授 (80342921)

Project Period (FY) 2018-06-29 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords過敏性亢進 / アレルギー / T細胞
Outline of Final Research Achievements

In allergic diseases, the hyperresponsiveness is developed in various organs, though the mechanism of its onset has not been elucidated. Based on our previous research, this study aimed to identify hyperresponsiveness-inducing factors by verifying the hypothesis "Molecules that are commonly produced / expressed by various T cell subsets cause hypersensitivity". Through the search for hyperresponsiveness-inducing factors, functional verification of candidate molecules, and re-evaluation of T cell-dependent hyperresponsiveness mouse models, we elucidated the possibility, with its underlying mechanisms, that neuropeptides produced by T cells are involved in the development of hyperresponsiveness. Furthermore, the requirement of reanalysis of the hyperresponsiveness-inducing factors, with considering the differences among the target organs as well as the biological responses, was suggested.

Academic Significance and Societal Importance of the Research Achievements

各種T細胞サブセットが共通して産生/発現する分過敏性亢進誘発因子を分子レベルで同定することは、過敏性亢進誘発因子を直接標的とした、これまでにない治療法の開発に直結しうる。それによりT細胞研究の新潮流を切り開き、アレルギー疾患領域に、新たなパラダイムシフトを生むことが強く期待される。本研究の成果は、それを基盤とした「免疫・神経・筋肉を包括したアレルギー疾患における過敏性亢進の発症機構解明」を目指した研究に昇華し、神経および平滑筋応答機構、マウスアレルギー疾患モデル、遺伝子改変技術の専門家に加え、過敏性亢進の臨床評価を続ける医療機関研究者も交えた包括的研究チームの立ち上げに結びついた。

Report

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

    (24 results)

All 2021 2020 2019 2018

All Journal Article (9 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 6 results) Presentation (15 results) (of which Int'l Joint Research: 8 results,  Invited: 3 results)

  • [Journal Article] T細胞依存的アレルギー性炎症の臓器・サブセット特異的な薬剤応答性2021

    • Author(s)
      神沼 修、三浦 健人、林 啓太朗、佐伯 真弓、廣井 隆親、森 晶夫
    • Journal Title

      アレルギーの臨床

      Volume: 41 Pages: 80-83

    • Related Report
      2020 Annual Research Report
  • [Journal Article] T Cell-Mediated Nasal Hyperresponsiveness in Allergic Rhinitis2020

    • Author(s)
      Osamu Kaminuma, Tomoe Nishimura, Mayumi Saeki, Akio Mori, Takachika Hiroi
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 43 Issue: 1 Pages: 36-40

    • DOI

      10.1248/bpb.b18-01021

    • NAID

      130007779207

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2020-01-01
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of CD4+ T Cells in Allergic Airway Diseases: Learning from Murine Models2020

    • Author(s)
      Miura Kento、Inoue Kimiko、Ogura Atsuo、Kaminuma Osamu
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 20 Pages: 7480-7480

    • DOI

      10.3390/ijms21207480

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] L-type amino acid transporter 1 (LAT1)-specific inhibitor is effective against T cell-mediated nasal hyperresponsiveness2020

    • Author(s)
      Kaminuma Osamu、Nishimura Tomoe、Saeki Mayumi、Yamasaki Norimasa、Ogata Sawako、Fujita Tomoe、Endou Hitoshi、Hayashi Keitaro
    • Journal Title

      Allergology International

      Volume: 69 Issue: 3 Pages: 455-458

    • DOI

      10.1016/j.alit.2019.12.006

    • NAID

      130007877710

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of pyrogallol from Awa-tea as an anti-allergic compound that suppresses nasal symptoms and IL-9 gene expression2020

    • Author(s)
      Nakano Tomohiro、Ikeda Mitsuhiro、Wakugawa Tomoharu、Kashiwada Yoshiki、Kaminuma Osamu、Kitamura Noriko、Yabumoto Masam、Fujino Hiromichi、Kitamura Yoshiaki、Fukui Hiroyuki、Takeda Noriaki、Mizuguchi Hiroyuki
    • Journal Title

      The Journal of Medical Investigation

      Volume: 67 Issue: 3.4 Pages: 289-297

    • DOI

      10.2152/jmi.67.289

    • NAID

      130007936857

    • ISSN
      1343-1420, 1349-6867
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] マウスTh9 細胞移入喘息モデルの解析からみえてきた新たな気道過敏性亢進機構2020

    • Author(s)
      佐伯 真弓、神沼 修、廣井 隆親
    • Journal Title

      日本薬理学雑誌

      Volume: 155 Pages: 375-380

    • NAID

      130007933869

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 皮膚アレルギー研究に役立つ新しいマウスモデル2020

    • Author(s)
      神沼 修、吉川 日出雄、森 晶夫
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 73 Pages: 506-512

    • Related Report
      2020 Annual Research Report
  • [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] Effects of anti-allergic drugs on T cell-mediated nasal hyperresponsiveness in a murine model of allergic rhinitis2018

    • Author(s)
      Nishimura Tomoe、Kaminuma Osamu、Saeki Mayumi、Kitamura Noriko、Gotoh Minoru、Mori Akio、Hiroi Takachika
    • Journal Title

      Allergology International

      Volume: 67 Issue: Supplement.1 Pages: S25-S31

    • DOI

      10.1016/j.alit.2018.05.002

    • NAID

      130007485137

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] T細胞依存性アレルギー性炎症に対するLAT1阻害薬の効果2021

    • Author(s)
      神沼修、佐伯真弓、西村友枝、廣井隆親、三浦健人、山崎憲政、尾形佐和子、伊藤大起、古山禎大、森晶夫、遠藤仁、安西尚彦、林啓太朗
    • Organizer
      第94回日本薬理学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Th9細胞移入マウスにおけるアレルギー性鼻粘膜炎症とステロイド抵抗性の解析2020

    • Author(s)
      古山禎大、三浦健人、山崎憲政、尾形佐和子、伊藤大起、森 晶夫、廣井隆親、佐伯真弓、神沼 修
    • Organizer
      アレルギー・好酸球研究会2020
    • Related Report
      2020 Annual Research Report
  • [Presentation] L型アミノ酸トランスポーター1阻害薬のTh2細胞依存性気管支喘息モデルに対する効果2020

    • Author(s)
      伊藤 大起、佐伯 真弓、三浦 健人、山崎 憲政、尾形 佐和子、古山 禎大、廣井 隆親、森 晶夫、遠藤 仁、林 啓太朗、神沼 修
    • Organizer
      アレルギー・好酸球研究会2020
    • Related Report
      2020 Annual Research Report
  • [Presentation] The contribution of L-type amino acid transporter 1 in activated Th2 cells for the development of atopic dermatitis2020

    • Author(s)
      Kaminuma O, Hayashi K, Nishimura T, Saeki M, Hiroi T, Iwata Y, Sugiura K, Mori A
    • Organizer
      JSA/WAO Joint Congress 2020
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Role of Costimulatory Signal in T Cell-Dependent Steroid-Resistant Asthma2020

    • Author(s)
      Mori A, Kouyama S, Yamaguchi M, Kumitani C, Ohtomo-Abe A, Ryu K, Nakamura Y, Hamada Y, Fujita N, Hayashi H, Watai K, Kamide Y, Sekiya K, Fukutomi Y, Taniguchi M, Matsumoto K, Tanimoto Y, Nobuyuki, Kobayashi N, Ohtomo T, Kaminuma O
    • Organizer
      ERS International Congress 2020
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Pharmacological analysis of helper T cell-dependent, steroid-resistant asthma2020

    • Author(s)
      Mori A, Kouyama S, Yamaguchi M, Kumitani C, Ohtomo-Abe A, Fujita N, Nagayama K, Iwata M, Ryu K, Nakamura Y, Hamada Y, Hayashi H, Watai K, Kamide Y, Sekiya K, Fukutomi Y, Taniguchi M, Ohtomo T, Kaminuma O
    • Organizer
      EAACI Congress 2020
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Th9 cells elicit bronchial hyperresponsiveness through eosinophil-independent mechanisms2020

    • Author(s)
      Saeki Mayumi, Kaminuma Osamu, Hiroi Takachika
    • Organizer
      第93回日本薬理学会年会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Differential mechanisms of Th2- and Th9-mediated bronchial hyperresponsiveness in mice2019

    • Author(s)
      Kaminuma Osamu, Saeki Mayumi, Nishimura Tomoe, Kitamura Noriko, Mori Akio, Hiroi Takachika
    • Organizer
      第68回日本アレルギー学会学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Pharmacological analysis of T cellinduced bronchoconstriction in vitro and in vivo2019

    • Author(s)
      Mori A, Kouyama S, Yamaguchi M, Kumitani C, Ohtomo-Abe A, Fujita N, Iwata M, Nagayama K, Ryu K, Nakamura Y, Tomita Y, Hamada Y, Hayashi H, Watai K, Kamide Y, Sekiya K, Fukutomi Y, Taniguchi M, Ohtomo T, Kaminuma O
    • Organizer
      European Academy of Allergy and Clinical Immunology Congress 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Pharmacological characterization of T cell-induced broncho-constriction2019

    • Author(s)
      constrictionMori A, Kouyama S, Yamaguchi M, Kumitani C, Ohtomo-Abe A, Fujita N, Iwata M, Nagayama K, Ryu K, Nakamura Y, Tomita Y, Hamada Y, Hayashi H, Watai K, Kamide Y, Sekiya K, Fukutomi Y, Taniguchi M, Ohtomo T, Kaminuma O
    • Organizer
      ATS International Conference 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Synergistic suppression of T cell-induced eosinophilia by glucocorticoid and CTLA4-Ig2019

    • Author(s)
      Mori A, Kouyama S, Yamaguchi M, Kumitani C, Ohtomo-Abe A, Fujita N, Iwata M, Nagayama K, Ryu K, Nakamura Y, Tomita Y, Hamada Y, Hayashi H, Watai K, Kamide Y, Sekiya K, Fukutomi Y, Taniguchi M, Ohtomo T, Kaminuma O
    • Organizer
      American Academy of Allergy Asthma & Immunology 2019 Annual Meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] T細胞の核移植によるアレルギー疾患モデルマウス2018

    • Author(s)
      神沼 修
    • Organizer
      第55回筑波実験動物研究会講演会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] アレルギー性鼻炎のメカニズムと抗原特異的免疫療法に対する実験動物学的解析2018

    • Author(s)
      神沼 修
    • Organizer
      第37回日本耳鼻咽喉科免疫アレルギー大会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Pharmacological characterization of T cell-induced broncho-constriction in vitro and in vivo2018

    • Author(s)
      Mori A, Kouyama S, Yamaguchi M, Kumitani C, Ohtomo-Abe A, Fujita N, Iwata M, Nagayama K, Ryu K, Nakamura Y, Tomita Y, Hamada Y, Hayashi H, Watai K, Kamide Y, Sekiya K, Fukutomi Y, Taniguchi M, Ohtomo T, Kaminuma O
    • Organizer
      RS International Congress 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Differential property of murine airway eosinophilic inflammation induced by Th2 and Th9 cells2018

    • Author(s)
      Saeki M, Kaminuma O, Nishimura T, Kitamura N, Mori A, Hiroi T
    • Organizer
      XXIV World Congress of Asthma
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

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Published: 2018-07-25   Modified: 2022-01-27  

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