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Elucidation and control of immune cell infiltration mechanism involved in the pathogenesis of allergic rhinitis.

Research Project

Project/Area Number 17K08785
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Experimental pathology
Research InstitutionHimeji Dokkyo University (2018-2019)
Shiga University of Medical Science (2017)

Principal Investigator

NAGAKUBO Daisuke  姫路獨協大学, 薬学部, 教授 (10368293)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsアレルギー性鼻炎 / 免疫細胞 / 細胞浸潤 / ケモカイン / CCL28 / 免疫学 / 炎症
Outline of Final Research Achievements

In this research project, by the allergic rhinitis mouse model, we found the importance of chemokine CCL28, a chemotaxis factor, for the migratory regulation of immune cells such as memory T cells, eosinophils, and IgA+ plasma cells, which play important roles in the pathogenesis of allergic rhinitis.
We also found that in the nasal mucosa, specialized neutrophils that exhibited an activated phenotype and a high level of phagocytotic activity were existing. These neutrophils were not observed in blood or other lymphoid tissues but were increased in the nasal mucosa due to the onset of allergic rhinitis.

Academic Significance and Societal Importance of the Research Achievements

アレルギー性鼻炎では、種々の免疫細胞が時系列に沿って鼻粘膜に動員され、それらが複雑に相互作用することで病態が形成される。アレルギー性鼻炎における免疫細胞の鼻粘膜浸潤の分子機構については詳細が不明であったが、本研究では、ケモカインCCL28がアレルギー性鼻炎の病態形成に重要な細胞群の動態制御に関わることを見出し、さらには鼻粘膜に貪食活性が極めて高い特殊な好中球が存在することを見出した。アレルギー性鼻炎の根本的治療法が限られている現状において、これらは新規の治療標的となる可能性を有しており、将来的な創薬などへの展開に繋がることが期待される。

Report

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

    (13 results)

All 2020 2019 2018 2017

All Journal Article (5 results) (of which Peer Reviewed: 4 results,  Open Access: 2 results) Presentation (8 results)

  • [Journal Article] A novel Siglec-F+ neutrophil subset in the mouse nasal mucosa exhibits an activated phenotype and is increased in an allergic rhinitis model2020

    • Author(s)
      Matsui Makoto、Nagakubo Daisuke、Satooka Hiroki、Hirata Takako
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 526 Issue: 3 Pages: 599-606

    • DOI

      10.1016/j.bbrc.2020.03.122

    • NAID

      120006839260

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A CCR4 antagonist enhances DC activation and homing to the regional lymph node and shows potent vaccine adjuvant activity through the inhibition of regulatory T-cell recruitment2018

    • Author(s)
      Yamamoto Shinya、Matsuo Kazuhiko、Nagakubo Daisuke、Higashiyama Shintaro、Nishiwaki Keiji、Oiso Naoki、Kawada Akira、Yoshie Osamu、Nakayama Takashi
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 136 Issue: 3 Pages: 165-171

    • DOI

      10.1016/j.jphs.2018.02.001

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] CCR4 Is Critically Involved in Skin Allergic Inflammation of BALB/c Mice2018

    • Author(s)
      Matsuo Kazuhiko、Nagakubo Daisuke、Komori Yuhei、Fujisato Shun、Takeda Natsumi、Kitamatsu Mizuki、Nishiwaki Keiji、Quan Ying-Shu、Kamiyama Fumio、Oiso Naoki、Kawada Akira、Yoshie Osamu、Nakayama Takashi
    • Journal Title

      Journal of Investigative Dermatology

      Volume: 138 Issue: 8 Pages: 1764-1773

    • DOI

      10.1016/j.jid.2018.02.027

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] CCL28-deficient mice have reduced IgA antibody-secreting cells and an altered microbiota in the colon2017

    • Author(s)
      Matsuo Kazuhiko、Nagakubo Daisuke、Yamamoto Shinya、Shigeta Akiko、Tomida Shuta、Fujita Mitsugu、Hirata Takako、Tsunoda Ikuo、Nakayama Takashi、Yoshie Osamu
    • Journal Title

      The Journal of Immunology

      Volume: 200 Issue: 2 Pages: 800-809

    • DOI

      10.4049/jimmunol.1700037

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] アレルギー性鼻炎におけるCD4+ T細胞の動態制御機構2017

    • Author(s)
      長久保 大輔
    • Journal Title

      アレルギーの臨床

      Volume: 37 Pages: 60-62

    • Related Report
      2017 Research-status Report
  • [Presentation] ケモカインによる粘液・唾液生成制御機構の解析2020

    • Author(s)
      海堀 祐一郎、松尾 一彦、中山 隆志、長久保 大輔
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ケモカイン受容体CCR4はメモリーTh17細胞増幅を介して乾癬発症に関与する2020

    • Author(s)
      北畑 孝祐、松尾 一彦、海堀 祐一郎、長久保 大輔、義江 修、中山 隆志
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] CCR4 is involved in psoriasis pathogenesis by inducing Th17 cell proliferation and skin-migration.2019

    • Author(s)
      Kitahata Kosuke、Matsuo Kazuhiko、Arima Yuka、Iwama Arisa、Nagakubo Daisuke、Yoshie Osamu、Nakayama Takashi
    • Organizer
      第48回 日本免疫学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 唾液・粘液生成の制御機構の解析2019

    • Author(s)
      海堀 祐一郎、小川 愛生、松尾 一彦、中山 隆志、長久保 大輔
    • Organizer
      第69回 日本薬学会関西支部総会・大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ケモカイン受容体 CCR4 を介した乾癬の病態形成メカニズムの解明2019

    • Author(s)
      北畑 孝祐、松尾 一彦、有馬 優香、岩間 有咲、 長久保 大輔、義江 修、中山 隆志
    • Organizer
      第69回 日本薬学会関西支部総会・大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 腸管での粘液産生におけるケモカインCCL28の影響の検討2018

    • Author(s)
      辰巳 蒼波、松尾 啓司、松尾 一彦、中山 隆志、長久保 大輔
    • Organizer
      第68回 日本薬学会近畿支部総会・大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Involvement of CCL28 in the pathogenesis of allergic rhinitis in a mouse model2017

    • Author(s)
      Nagakubo Daisuke、Matsui Makoto、Satooka Hiroki、Sato Tomomi、Matsuo Kazuhiko、Yamamoto Shinya、Nakayama Takashi、Yoshie Osamu、Hirata Takako
    • Organizer
      第46回日本免疫学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Role of neutrophils in the nasal mucosa in a mouse model of allergic rhinitis2017

    • Author(s)
      Matsui Makoto、Nagakubo Daisuke、Satooka Hiroki、Hirata Takako
    • Organizer
      第46回日本免疫学会学術集会
    • Related Report
      2017 Research-status Report

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

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