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Elucidation of mechanisms how M2 macrophages induced by basophils dampen excess inflammation

Research Project

Project/Area Number 18K15180
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 49070:Immunology-related
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Miyake Kensuke  東京医科歯科大学, 大学院医歯学総合研究科, 特任助教 (90814533)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords好塩基球 / M2マクロファージ / IL-4 / 死細胞 / IL-1α / 炎症抑制 / アレルギー / 免疫学 / 好中球 / アレルギー炎症 / マクロファージ
Outline of Final Research Achievements

Elucidation of the pathophysiology of chronic allergic inflammation is the urgent problem in developed countries. Especially, the mechanisms for the termination of allergic inflammation remains ill-defined. Our group previously identified that basophils contribute to the termination of allergic inflammation by inducing the differentiation of anti-inflammatory M2-like macrophages.In this study, we investigated the molecular mechanisms how basophils and anti-inflammatory M2 macrophages dampen excess allergic inflammation. We discovered that activated basophils release IL-4 and enhance the capacity of dead cell clearance in M2 macrophages, thus preventing the aggravation of allergic inflammation caused by dead cell-derived mediators, including IL-1α.

Academic Significance and Societal Importance of the Research Achievements

これまでのアレルギー研究では、アレルギー炎症の誘導機構に重点が置かれ、発症に関与する分子がアレルギー疾患の治療標的とされてきた。しかしながらこの治療法では、すでに発症したアレルギー炎症の治療には有効ではない可能性が高い。アレルギー炎症の終息機構が解明できれば、アレルギーが発症している最中であっても炎症を終息させアレルギー症状を改善できる画期的な治療法の開発が期待される。本研究により、好塩基球やM2マクロファージによるアレルギー炎症の終息機構の一端が解明された。この研究を応用すれば、アレルギーの新規治療法開発につながると考えられ、社会的・学術的に大きな意義を持つ研究である。

Report

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

    (24 results)

All 2020 2019 2018 2017 Other

All Int'l Joint Research (2 results) Journal Article (12 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 7 results,  Open Access: 3 results) Presentation (10 results) (of which Int'l Joint Research: 2 results)

  • [Int'l Joint Research] CVPath Institute(米国)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] University of Cape Town(南アフリカ)

    • Related Report
      2018 Research-status Report
  • [Journal Article] Tolerogenic properties of CD206+ macrophages appeared in the sublingual mucosa after repeated antigen-painting.2020

    • Author(s)
      Yang Y, Nagai S, Kang S, Xia Y, Kawano Y, Miyake K, Karasuyama H, Azuma M.
    • Journal Title

      International Immunology

      Volume: - Issue: 8 Pages: 509-518

    • DOI

      10.1093/intimm/dxaa014

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 【アレルギーのエフェクター細胞研究の進展】好塩基球2020

    • Author(s)
      三宅 健介, 吉川 宗一郎, 柴田 翔, 山西 吉典, 烏山 一.
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 73 Pages: 6-13

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Pivotal role of STIM2, but not STIM1, in IL-4 production by IL-3?stimulated murine basophils2019

    • Author(s)
      Yoshikawa Soichiro、Oh-hora Masatsugu、Hashimoto Ryota、Nagao Toshihisa、Peters Louis、Egawa Mayumi、Ohta Takuya、Miyake Kensuke、Adachi Takahiro、Kawano Yohei、Yamanishi Yoshinori、Karasuyama Hajime
    • Journal Title

      Science Signaling

      Volume: 12 Issue: 576

    • DOI

      10.1126/scisignal.aav2060

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 好塩基球による、トロゴサイトーシスを介した新たな抗原提示メカニズム2019

    • Author(s)
      三宅 健介, 烏山 一
    • Journal Title

      感染・炎症・免疫

      Volume: 49 Pages: 61-64

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Th2型免疫応答における好塩基球の役割2019

    • Author(s)
      三宅 健介、 吉川 宗一郎、 山西 吉典、烏山 一
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 71 Pages: 177-184

    • NAID

      40021798131

    • Related Report
      2018 Research-status Report
  • [Journal Article] Histamine Released From Skin-Infiltrating Basophils but Not Mast Cells Is Crucial for Acquired Tick Resistance in Mice2018

    • Author(s)
      Tabakawa Yuya、Ohta Takuya、Yoshikawa Soichiro、Robinson Elisabeth J.、Yamaji Kayoko、Ishiwata Kenji、Kawano Yohei、Miyake Kensuke、Yamanishi Yoshinori、Ohtsu Hiroshi、Adachi Takahiro、Watanabe Naohiro、Kanuka Hirotaka、Karasuyama Hajime
    • Journal Title

      Frontiers in Immunology

      Volume: 9

    • DOI

      10.3389/fimmu.2018.01540

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] How do basophils contribute to Th2 cell differentiation and allergic responses?2018

    • Author(s)
      Karasuyama Hajime、Miyake Kensuke、Yoshikawa Soichiro、Kawano Yohei、Yamanishi Yoshinori
    • Journal Title

      International Immunology

      Volume: 30 Issue: 9 Pages: 391-396

    • DOI

      10.1093/intimm/dxy026

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Basophils trigger emphysema development in a murine model of COPD through IL-4?mediated generation of MMP-12?producing macrophages2018

    • Author(s)
      Shibata Sho、Miyake Kensuke、Tateishi Tomoya、Yoshikawa Soichiro、Yamanishi Yoshinori、Miyazaki Yasunari、Inase Naohiko、Karasuyama Hajime
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 115 Issue: 51 Pages: 13057-13062

    • DOI

      10.1073/pnas.1813927115

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Aggregation makes a protein allergenic at the challenge phase of basophil-mediated allergy in mice2018

    • Author(s)
      Nagao Toshihisa、Yamanishi Yoshinori、Miyake Kensuke、Teranishi Mio、Takahashi Saori、Yoshikawa Soichiro、Kawano Yohei、Karasuyama Hajime
    • Journal Title

      International Immunology

      Volume: 31 Issue: 1 Pages: 41-49

    • DOI

      10.1093/intimm/dxy062

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] 免疫学のABC(第8回) 顆粒球の作用と役割2018

    • Author(s)
      三宅 健介
    • Journal Title

      分子リウマチ治療

      Volume: 11 Pages: 148-151

    • NAID

      40021650431

    • Related Report
      2018 Research-status Report
  • [Journal Article] トロゴサイトーシスを介した好塩基球による抗原提示機構2018

    • Author(s)
      三宅 健介、 山西吉典、 烏山 一
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 70 Pages: 623-630

    • NAID

      40021747556

    • Related Report
      2018 Research-status Report
  • [Journal Article] Multifaceted roles of basophils in health and disease2017

    • Author(s)
      Karasuyama H, Miyake K, Yoshikawa S, Yamanishi Y
    • Journal Title

      J Allergy Clin Immunol

      Volume: S0091-6749 Issue: 2 Pages: 31894-31898

    • DOI

      10.1016/j.jaci.2017.10.042

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 慢性閉塞性肺疾患(COPD)患者の肺組織に好塩基球が浸潤している2019

    • Author(s)
      柴田 翔, 立石 知也, 小林 正嗣, 大久保 憲一, 明石 巧, 三宅 健介, 山西 吉典, 烏山 一, 宮崎 泰成
    • Organizer
      第68回日本アレルギー学会学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 好塩基球は炎症抑制型のM2マクロファージを誘導することで、アレルギー炎症の悪化を妨げる2019

    • Author(s)
      三宅 健介
    • Organizer
      2019年先端モデル動物支援若手技術支援講習会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Basophils promote the differentiation of monocytes into M2-like macrophages which dampen IL-1α-mediated aggravation of allergic inflammation2019

    • Author(s)
      Miyake K, Yoshikawa S, Yamanishi Y, Karasuyama H.
    • Organizer
      17th IUIS 2019 (International Congress of Immunology)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Pivotal role of STIM2, but not STIM1, in IL-4 production by IL-3-stimulated basophils2019

    • Author(s)
      Yoshikawa S, Oh-hora M, Hashimoto R, Miyake K, Adachi T, Kawano Y, Yamanish Y, Kamiya A, Karasuyama H
    • Organizer
      17th IUIS 2019 (International Congress of Immunology)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Monocyte-derived M2-like macrophages induced by activated basophils dampen IL-1α-mediated aggravation of allergic inflammation2019

    • Author(s)
      Miyake K, Yoshikawa S, Yamanishi Y, Karasuyama H
    • Organizer
      The 48th Annual Meeting of The Japanese Society for Immunology
    • Related Report
      2019 Annual Research Report
  • [Presentation] Identification of immature-type basophils that are distinguishable from mature ones in terms of surface phenotype and activation property2019

    • Author(s)
      Ito J, Miyake K, Shichino S, Yamanishi Y, Karasuyama H
    • Organizer
      The 48th Annual Meeting of The Japanese Society for Immunology
    • Related Report
      2019 Annual Research Report
  • [Presentation] Basophil-derived IL-4 promotes disease progression in a hapten-elicited murine model of atopic dermatitis2019

    • Author(s)
      Mogi K, Takahashi K, Miyake K, Yoshikawa S, Karasuyama H, Yamanishi Y
    • Organizer
      The 48th Annual Meeting of The Japanese Society for Immunology
    • Related Report
      2019 Annual Research Report
  • [Presentation] Basophils promote monocyte differentiation to M2-like macrophages that display enhanced capacity of allergen clearance.2018

    • Author(s)
      Kensuke Miyake、 Ayako Fukui、 Soichiro Yoshikawa、 Yoshinori Yamanishi、 Hajime Karasuyama
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Aggregation makes a protein allergenic at the challenge phase of basophil-mediated allergy in mice.2018

    • Author(s)
      Toshihisa Nagao、 Yoshinori Yamanishi、 Kensuke Miyake、 Mio Teranishi、 Soichiro Yoshikawa、 Yohei Kawano、 Hajime Karasuyama
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Histamine Released From Skin-Infiltrating Basophils but not mast cells is crucial for acquired tick resistance in mice.2018

    • Author(s)
      Soichiro Yoshikawa、 Yuya Tabakawa、 Takuya Ohta、 Kayoko Yamaji、 Kenji Ishiwata、 Yohei Kawano、Yoshinori Yamanishi,、Hiroshi Ohtsu、Takahiro Adachi、 Naohiro Watanabe、 Hirotaka Kanuka、 Hajime Karasuyama
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2021-02-19  

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