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Establishment and application of mouse and human phagocytes using differentiation reprogram

Research Project

Project/Area Number 15H04717
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionKanazawa Medical University (2016-2017)
Tokyo Medical and Dental University (2015)

Principal Investigator

Onai Nobuyuki  金沢医科大学, 医学部, 教授 (50323605)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2017: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2015: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywords樹状細胞 / 前駆細胞 / 転写因子 / 分化 / 単核貪食細胞 / 免疫学 / 単核性貪食細胞 / マクロファージ / 単球 / 分化リプログラム / 貪食細胞 / リプログラム
Outline of Final Research Achievements

Dendritic cells (DCs) are consisted conventional DCs and plasmacytoid DC (pDCs) which have antigen presentation capacity and type-I interferon producing capacity, respectively. In this study, we generate E2-2 reporter mouse which is essential transcription factor for pDC development. Using this mouse, we identified E2-2high and E2-2lo cells in th common DC progenitor (CDPs). E2-2highCDPs develop only pDC in vivo in the spleen, however, in the small intestine, some E2-2highCDPs develop into cDC. This trans-differentiation is mediated by IL-3, IL-5, GM-CSF (all enriched in the gut tissue). In ex vivo cultures with Flt3L+GM-CSF, E2-2highCDPs derived cDCs, but not pDCs, induce Foxp3+ Treg. E2-2 is therefore important in committing pDC differentiation but conversion to cDCs can occur in the intestine and modulate regulatory environment there.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (14 results)

All 2017 2016 Other

All Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 4 results,  Acknowledgement Compliant: 2 results) Presentation (5 results) (of which Int'l Joint Research: 4 results) Book (1 results) Remarks (2 results)

  • [Journal Article] Flexible fate commitment of E2-2high common DC progenitors implies tuning in tissue microenvironments2017

    • Author(s)
      Onai Nobuyuki、Asano Jumpei、Kurosaki Rumiko、Kuroda Shoko、Ohteki Toshiaki
    • Journal Title

      International Immunology

      Volume: 29 Issue: 10 Pages: 443-456

    • DOI

      10.1093/intimm/dxx058

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mast cell hyperactivity underpins the development of oxygen-induced retinopathy.2017

    • Author(s)
      Matsuda K, Okamoto N, Kondo M, Arkwright PD, Karasawa K, Ishizaka S, Yokota S, Matsuda A, Jung K, Oida K, Amagai Y, Jang H, Noda E, Kakinuma R, Yasui K, Kaku U, Mori Y, Onai N, Ohteki T, Tanaka A, Matsuda H
    • Journal Title

      J. Clin. Invest.

      Volume: 127 Issue: 11 Pages: 3987-4000

    • DOI

      10.1172/jci89893

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Intrinsic autophagy is required for the maintenance of intestinal stem cells and for irradiation-induced intestinal regeneration.2017

    • Author(s)
      Asano J, Sato T, Ichinose S, Kajita M, Onai N, Shimizu S, Ohteki T.
    • Journal Title

      Cell reports

      Volume: 20 Issue: 5 Pages: 1050-1060

    • DOI

      10.1016/j.celrep.2017.07.019

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of a human clonogenic progenitor with strict monocyte differentiation potential: A counterpart of mouse cMoPs2017

    • Author(s)
      Kawamura S, Onai N, Miya F, Sato T, Tsunoda T, Kurabayashi K, Yotsumoto S, Kuroda S, Takenaka K, Akashi K, Ohteki T
    • Journal Title

      Immunity

      Volume: 46 Issue: 5 Pages: 835-848

    • DOI

      10.1016/j.immuni.2017.04.019

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Identification of a human clonogenic progenitor with strict monocyte differentiation potential - a counterpart of mouse cMoPs.2017

    • Author(s)
      Kawamura S, Onai N, Kurabayashi K, Sato T, Miya F, Tsunoda, T, Yotsumoto S, Kuroda S, Takenaka K, Akashi K, Ohteki T.
    • Journal Title

      Immunity

      Volume: 未定

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Cytosine-phosphorothionate- guanine oligodeoxynucleotides exacerbates hemophagocytosis by inducing tumor necrosis factor-α production in mice after bone marrow transplanation.2016

    • Author(s)
      Liu J, Guo YM, Onai N, Ohyagi H, Hirokawa M, Takahashi N, Tagawa H, Ubukawa K, Kobayahi I, Tezuka H, Minamiya Y, Ohteki T, and Sawada K.
    • Journal Title

      Biol Blood Marrow Transplant 2015

      Volume: 印刷中 Issue: 4 Pages: 627-636

    • DOI

      10.1016/j.bbmt.2015.12.018

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Identification of Flt3-ligand producing cells by generating Flt3-ligand mCherry reporter mouse.2017

    • Author(s)
      Nobuyuki Onai and Toshiaki Ohteki.
    • Organizer
      5th Annual Meeting of the international Cytokine and Interferon Society.
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Involvement of poly-rC binding proteins in posttranscriptional regulation of Sortilin, the cytokine trafficking mediator.2017

    • Author(s)
      Toshiki Yabe-Wada, Shintaro Matsuba, Kazuya Takeda, Akira Nakamura, Haifeng Shi, Caroline C. Philpott, Nobuyuki Onai.
    • Organizer
      5th Annual Meeting of the international Cytokine and Interferon Society.
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Regulation of pDC development by graded expression of E2-2.2017

    • Author(s)
      Nobuyuki Onai and Toshiaki Ohteki.
    • Organizer
      The 46th Annual Meeting of The Japanese Society for Immunology.
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] SLPI negatively regulates LPS-induced eosinophil activation via inhibition of Elk-1 phosphorylation.2017

    • Author(s)
      4.Shintaro Matsuba, Toshiki Yabe-Wada, Kazuya Takeda, Nobuyuki Onai, Toshiyuki Takai, Akira Nakamura.
    • Organizer
      The 46th Annual Meeting of The Japanese Society for Immunology.
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Regulation of pDC development by graded expression of E2-2.2017

    • Author(s)
      Nobuyuki Onai, Junpei Asano, Shoko Kuroda, and Toshiaki Ohteki.
    • Organizer
      第27回 日本樹状細胞研究会.
    • Related Report
      2017 Annual Research Report
  • [Book] “Isolation of mouse dendritic cell progenitor and bone marrow progenitor”. Methods Mol. Biol.2016

    • Author(s)
      Onai N & Ohteki T
    • Total Pages
      8
    • Publisher
      Human Press, UK
    • Related Report
      2015 Annual Research Report
  • [Remarks] 金沢医科大学医学部免疫学講座ホームページ

    • URL

      http://www.kanazawa-med.ac.jp/~serol/Immunology/Top_Page.html

    • Related Report
      2017 Annual Research Report
  • [Remarks] 東京医科歯科大学難治疾患研究所生体防御学分野ホームページ

    • URL

      http://www.tmd.ac.jp/mri/bre/index.html

    • Related Report
      2016 Annual Research Report

URL: 

Published: 2015-04-16   Modified: 2019-03-29  

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