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Elucidation of the mechanisms to induce eosinophilic inflammation through ILC2s in allergic rhinitis

Research Project

Project/Area Number 17K16908
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Otorhinolaryngology
Research InstitutionShiga University of Medical Science

Principal Investigator

Tojima Ichiro  滋賀医科大学, 医学部, 講師 (80567347)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsアレルギー性鼻炎 / 2型自然リンパ球 / システイニルロイコトリエン / プロスタグランジンD2 / 好酸球 / ラマトロバン / モンテルカスト / ハウスダスト / ILC2 / CRTH2 / CysLT1 / アレルギー・ぜんそく
Outline of Final Research Achievements

Prevalence of ILC2s in the inferior nasal turbinate (INT) tissues and the activating mechanisms of ILC2s were examined in patients with house dust mites (HDM)-induced allergic rhinitis (AR). The prevalence of ILC2s was increased in nasal mucosa of patients with HDM-induced AR, and it was positively correlated with the number of infiltrating eosinophils. ILC2s in the INT tissues expressed a prostaglandin D2 (PGD2) receptor, chemoattractant receptor-homologous molecule expressed TH2 cells (CRTH2), and a cysteinyl leukotrienes (cysLTs) receptor, CysLT1. After nasal provocation test, the number of eosinophils and concentrations of PGD2 and cysLTs were increased in the nasal lavage fluid from AR patients. PGD2 and cysLTs induced IL-5 production from cultured PBMC-derived ILC2s. PGD2-induced and cysLTs-induced production of IL-5 and IL-13 from ILC2s was completely inhibited by ramatroban, a dual CRTH2 and thromboxane receptor antagonist, and montelukast, a CysLT1 antagonist, respectively.

Academic Significance and Societal Importance of the Research Achievements

アレルギー性鼻炎単独の病態において、鼻粘膜中の2型自然リンパ球がアレルゲン刺激により即時相で産生されたプロスタグランジンD2とシステイニルロイコトリエンに反応してIL-5やIL-13を産生し、好酸球遊走に働く事を初めて明らかにすることで、アレルギー性鼻炎の病態の一端を解明した。これらの刺激はラマトロバン、モンテルカストにより抑制されるため、治療薬の新たな作用機序を明らかにしたことにもつながる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (14 results)

All 2020 2019 2018 2017

All Journal Article (6 results) (of which Peer Reviewed: 4 results) Presentation (8 results) (of which Int'l Joint Research: 3 results,  Invited: 2 results)

  • [Journal Article] Immunological effects of sublingual immunotherapy with Japanese cedar pollen extract in patients with combined Japanese cedar and Japanese cypress pollinosis2020

    • Author(s)
      Kikuoka Hirotaka、Kouzaki Hideaki、Matsumoto Koji、Arai Hiroyuki、Yamamoto Sayuri、Tojima Ichiro、Shimizu Shino、Miyashita Hiromi、Ogawa Yukiko、Osada Toshihiro、Okano Mitsuhiro、Yuta Atsushi、Shimizu Takeshi
    • Journal Title

      Clinical Immunology

      Volume: 210 Pages: 108310-108310

    • DOI

      10.1016/j.clim.2019.108310

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 特集 スギ・ヒノキ花粉症 最新の話題 Ⅱ.病因論に関する話題 3.ILC2とアレルギー性鼻炎2019

    • Author(s)
      戸嶋一郎、清水猛史
    • Journal Title

      アレルギー・免疫

      Volume: 26 Issue: 2 Pages: 172-179

    • DOI

      10.20837/3201902172

    • ISSN
      1344-6932
    • Year and Date
      2019-01-15
    • Related Report
      2019 Annual Research Report 2018 Research-status Report
  • [Journal Article] Evidence for the induction of Th2 inflammation by group 2 innate lymphoid cells in response to prostaglandin D 2 and cysteinyl leukotrienes in allergic rhinitis2019

    • Author(s)
      Tojima Ichiro、Matsumoto Koji、Kikuoka Hirotaka、Hara Shiori、Yamamoto Sayuri、Shimizu Shino、Kouzaki Hideaki、Shimizu Takeshi
    • Journal Title

      Allergy

      Volume: 74 Issue: 12 Pages: 2417-2426

    • DOI

      10.1111/all.13974

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Group 2 innate lymphoid cells and eosinophilic chronic rhinosinusitis2019

    • Author(s)
      Tojima Ichiro、Shimizu Takeshi
    • Journal Title

      Current Opinion in Allergy and Clinical Immunology

      Volume: 19 Issue: 1 Pages: 18-25

    • DOI

      10.1097/aci.0000000000000496

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Arachidonic acid metabolites-induced activation of group 2 innate lymphoid cell in eosinophilic upper airway inflammation2019

    • Author(s)
      Tojima Ichiro、Shimizu Takeshi
    • Journal Title

      Journal of Japan Society of Immunology & Allergology in Otolaryngology

      Volume: 37 Issue: 3 Pages: 217-222

    • DOI

      10.5648/jjiao.37.217

    • NAID

      130007709690

    • ISSN
      0913-0691, 2185-5900
    • Related Report
      2019 Annual Research Report
  • [Journal Article] In vitro and in vivo inhibitory effects of TLR4 agonist, glucopyranosyl lipid A (GLA), on allergic rhinitis caused by Japanese cedar pollen2019

    • Author(s)
      Matsumoto Koji、Kouzaki Hideaki、Yamamoto Sayuri、Kikuoka Hirotaka、Tojima Ichiro、Meulen Jan H.、Shimizu Takeshi
    • Journal Title

      Allergy

      Volume: 75 Issue: 2 Pages: 446-449

    • DOI

      10.1111/all.13989

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Presentation] 上気道の好酸球性炎症における脂質メディエーターを介した2型自然リンパ球活性化機構2019

    • Author(s)
      戸嶋一郎
    • Organizer
      第37回日本耳鼻咽喉科免疫アレルギー学会
    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Invited
  • [Presentation] ILC2s in eosinophilic chronic rhinosinusitis and allergic rhinitis2019

    • Author(s)
      Ichiro Tojima
    • Organizer
      57th Korean Rhinologic Society
    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] The role of group 2 innate lymphoid cells (ILC2s) in the pathogenesis of allergic rhinitis2018

    • Author(s)
      Ichiro Tojima
    • Organizer
      第67回日本アレルギー学会
    • Related Report
      2018 Research-status Report
  • [Presentation] アレルギー性鼻炎における脂質メディエーターを介した鼻粘膜2型自然リンパ球の役割2018

    • Author(s)
      戸嶋一郎
    • Organizer
      第57回日本鼻科学会
    • Related Report
      2018 Research-status Report
  • [Presentation] The Role of Group 2 Innate Lymphoid Cells (ILC2s) in the Pathogenesis of Allergic Rhinitis2018

    • Author(s)
      Ichiro Tojima
    • Organizer
      ILC2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] アレルギー性鼻炎におけるgroup 2 innate lymphoid cells (ILC2)の役割2018

    • Author(s)
      戸嶋一郎
    • Organizer
      第36回日本耳鼻咽喉科免疫アレルギー学会
    • Related Report
      2017 Research-status Report
  • [Presentation] アレルギー性鼻炎の好酸球遊走機構におけるILC2の関与2017

    • Author(s)
      戸嶋一郎
    • Organizer
      第56回日本鼻科学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Role of group 2 innate lymphoid cells (ILC2s) during eosinophil infiltration in allergic rhinitis2017

    • Author(s)
      Ichiro Tojima
    • Organizer
      The 3rd Rhinology Research Forum in Asia (RReFA)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2021-02-19  

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