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Comprehensive understanding of dendritic cell progenitor and its therapeutic application basis

Research Project

Project/Area Number 26253029
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionTokyo Medical and Dental University

Principal Investigator

OHTEKI Toshiaki  東京医科歯科大学, 難治疾患研究所, 教授 (50233200)

Co-Investigator(Renkei-kenkyūsha) ONAI Nobuyuki  東京医科歯科大学, 難治疾患研究所, 講師 (50323605)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥40,300,000 (Direct Cost: ¥31,000,000、Indirect Cost: ¥9,300,000)
Fiscal Year 2016: ¥13,130,000 (Direct Cost: ¥10,100,000、Indirect Cost: ¥3,030,000)
Fiscal Year 2015: ¥13,130,000 (Direct Cost: ¥10,100,000、Indirect Cost: ¥3,030,000)
Fiscal Year 2014: ¥14,040,000 (Direct Cost: ¥10,800,000、Indirect Cost: ¥3,240,000)
Keywords樹状細胞 / E2-2 / pDC / cDC / CDP / CD103陽性cDC / Treg / 免疫寛容 / 分化転換 / ALDH / 免疫学 / 組織・細胞 / 生体分子 / IRF8 / 樹状細胞(DC) / DC前駆細胞(CDP) / 従来型DC(cDC) / 形質細胞様DC(pDC) / CDPニッチ
Outline of Final Research Achievements

Transcription factor E2-2 is essential for the development of plasmacytoid dendritic cells (pDCs) but not conventional DCs (cDCs). In this study, we generated E2-2 reporter mice and demonstrated that an E2-2high fraction among common DC progenitors (CDPs) strictly gave rise to pDCs in the presence of Flt3 ligand ex vivo or in the secondary lymphoid organs when transferred in vivo. However, in the small intestine, some of these E2-2high progenitors differentiated into cDCs that produced retinoic acid. This transdifferentiation was driven by signaling via the common β receptor, a receptor for the cytokines IL-3, IL-5 and GM-CSF, which are abundant in the gut. In the presence of GM-CSF and Flt3 ligand, E2-2high-progenitor-derived cDCs consistently induced Foxp3+ regulatory T cells ex vivo. Our findings reveal the commitment and flexibility of E2-2high progenitor differentiation, and imply that pertinent tuning machinery is present in the gut microenvironment.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (20 results)

All 2017 2016 2015 2014 Other

All Journal Article (10 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 7 results,  Acknowledgement Compliant: 3 results,  Open Access: 4 results) Presentation (7 results) (of which Int'l Joint Research: 2 results,  Invited: 5 results) Book (2 results) Remarks (1 results)

  • [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
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] マクロファージの分化と多様性「免疫学のABC」 第2回2017

    • Author(s)
      樗木俊聡
    • Journal Title

      分子リウマチ治療2

      Volume: 10 Pages: 46-49

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Non-myeloablative preconditioning with ACK2 (anti-c-kit antibody) is efficient in bone marrow transplantation for murine models of mucopolysaccharidosis type II2016

    • Author(s)
      Yokoi, T., Yokoi, K., Akiyama, K., Higuchi, T., Shimada, Y., Kobayashi, H., Sato, T., Ohteki, T., Otsu, M., Nakauchi, H., Ida, H. and Ohashi, T
    • Journal Title

      Mol Genet Meta

      Volume: 119 Issue: 3 Pages: 232-238

    • DOI

      10.1016/j.ymgme.2016.08.003

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Isolation of dendritic cell progenitor and bone marrow progenitor cells from mouse.2016

    • Author(s)
      Onai N, Ohteki T.
    • Journal Title

      Methods Mol Biological

      Volume: 1423 Pages: 53-59

    • DOI

      10.1007/978-1-4939-3606-9_4

    • ISBN
      9781493936045, 9781493936069
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 樹状細胞前駆細胞および樹状細胞サブセットのソーティング2016

    • Author(s)
      小内伸幸、樗木俊聡
    • Journal Title

      実験医学  最強のステップUPシリーズ 新版!フローサイトメトリー

      Volume: 別冊 Pages: 229-240

    • Related Report
      2016 Annual Research Report
  • [Journal Article] マクロファージ・樹状細胞の起源と多様性2016

    • Author(s)
      樗木俊聡
    • Journal Title

      医学のあゆみ マクロファージのすべて

      Volume: 259 Pages: 247-352

    • Related Report
      2016 Annual Research Report
  • [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
  • [Journal Article] Commensal Gram-positive bacteria initiates colitis by inducing monocyte/macrophage mobilization2015

    • Author(s)
      Yusuke Nakanishi, Taku Sato, and Toshiaki Ohteki.
    • Journal Title

      Mucosal Immunology

      Volume: 8 Issue: 1 Pages: 152-160

    • DOI

      10.1038/mi.2014.53

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bacterial c-di-GMP affects hematopoietic stem/progenitors and their niches through STING.2015

    • Author(s)
      Kobayashi H, Kobayashi CI, Nakamura-Ishizu A, Karigane D, Haeno H, Yamamoto KN, Sato T, Ohteki T, Hayakawa Y, Barber GN, Kurokawa M, Suda T, and Takubo K.
    • Journal Title

      Cell Reports

      Volume: 111 Issue: 1 Pages: 71-84

    • DOI

      10.1016/j.celrep.2015.02.066

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Bipotent or Oligopotent? A macrophage and DC progenitor revisited.2014

    • Author(s)
      Onai, N. and Ohteki, T.
    • Journal Title

      Immunity

      Volume: 41 Issue: 1 Pages: 5-7

    • DOI

      10.1016/j.immuni.2014.07.004

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 免疫・細胞治療の基礎と応用2016

    • Author(s)
      樗木俊聡
    • Organizer
      相馬市歯科医師会地域学術講演会
    • Place of Presentation
      福島県相馬市 相馬フローラ
    • Year and Date
      2016-09-10
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Identification of mononuclear phagocyte progenitors.2015

    • Author(s)
      Ohteki T.
    • Organizer
      The 44th Annual Meeting of the Japanese Society for Immunology
    • Place of Presentation
      北海道札幌市(札幌コンベンションセンター)
    • Year and Date
      2015-11-18
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 「免疫の司令塔、樹状細胞の源となる細胞の同定」2015

    • Author(s)
      樗木俊聡
    • Organizer
      第22回輸血細胞治療学会シンポジウム
    • Place of Presentation
      長野件北佐久郡(軽井沢プリンスホテル)
    • Year and Date
      2015-10-23
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Identity and flexibility of common dendritic cell progenitor.2015

    • Author(s)
      Ohteki T.
    • Organizer
      4th Europian Congress of Immunology
    • Place of Presentation
      ウィーン(オーストリア)
    • Year and Date
      2015-09-06
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 免疫の司令塔、樹状細胞を大量に生み出す減細胞の同定2014

    • Author(s)
      樗木 俊聡
    • Organizer
      第14回難治性免疫疾患先端治療開発研究会
    • Place of Presentation
      東京
    • Year and Date
      2014-12-05
    • Related Report
      2014 Annual Research Report
  • [Presentation] Dendritic cell and immune regulation.2014

    • Author(s)
      樗木 俊聡
    • Organizer
      The 2014 Fall Conference of the KAI
    • Place of Presentation
      ソウル
    • Year and Date
      2014-11-06 – 2014-11-07
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Novel Source of Dendritic Cells, the Control Tower of the Immune System.2014

    • Author(s)
      樗木 俊聡
    • Organizer
      Novo Nordisk Innavation Summit Tokyo 2014
    • Place of Presentation
      東京
    • Year and Date
      2014-10-01
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Book] Annual Review 血液(2015)2015

    • Author(s)
      樗木俊聡
    • Total Pages
      285
    • Publisher
      中外医学社
    • Related Report
      2015 Annual Research Report
  • [Book] Annual Review 2015 呼吸器2015

    • Author(s)
      樗木俊聡
    • Total Pages
      252
    • Publisher
      中外医学社
    • Related Report
      2014 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 2015 Annual Research Report

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Published: 2014-04-04   Modified: 2018-03-22  

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