Identification of mouse and human DC progenitor

• Project/Area Number: 24590576
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: ONAI Nobuyuki 東京医科歯科大学, 難治疾患研究所, 講師 (50323605)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 樹状細胞 / 前駆細胞 / サイトカイン / 免疫 / ヒト化マウス

Outline of Final Research Achievements

Dendritic cells (DCs) are professional antigen and induce immune response. In the second lymphoid organ, DCs are subdivided into two sunsets: conventional DCs (cDCs) and plasmacytoid DCs (pDCs). Previously, we identified DC-restricted progenitors, CDPs based on the cytokine receptors expressions. The CDPs gave rise to many cDCs but poor pDC developmental potential. In this study, we identified new DC progenitor with prominent pDC development potential. The new DC progenitor highly expressed E2-2, which is essential transcription factor for pDC development. The new DC progenitors gave rise to only DC sunsets but no other lineages. Based on these data, we proposed the CDPs are comprised of two progenitors: CD115+ and CD115- CDPs. Furthermore, we found that lympho-primed multipotent progenitors (LMPPs) directly give rise to both CD115+ and CD115- CDPs in vivo. These results revised load map of DC development and shed new light on the immunology and hematopoiesis.

Research Products

• [Journal Article] Dendritic cells, monocytes and macrophages: a unified nomenclature based on ontogeny. (2014)
  • Author(s): Guilliams, M, Ginhoux, F, Jakubzick, C, Naik, S.H., Onai, N., Schraml, B.U., Segura, E., Tussiwand, R., and Yona, S.
  • Journal Title: Nat.Rev. Immunol. Volume: 14 Issue: 8 Pages: 571-578
  • DOI: 10.1038/nri3712
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [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
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Monocyte-derived dendritic cells perform hemophagocytosis to fine-tune excessive immune responses. (2013)
  • Author(s): Ohyagi H, Onai N, Sato T., et al.
  • Journal Title: Immunity Volume: 39 Pages: 584-598
  • NAID: 40020181881
  • Peer Reviewed
• [Journal Article] A Clonogenic Progenitor with Prominent Plasmacytoid Dendritic Cell Developmental Potential (2013)
  • Author(s): Onai, N., Kurabayashi, K., Hosoi-Amaike, M., Toyama-Sorimachi, N., Matsushima, K., Inaba, K. and Ohteki T
  • Journal Title: Immunity Volume: (in press) Issue: 5 Pages: 943-957
  • DOI: 10.1016/j.immuni.2013.04.006
  • Peer Reviewed
• [Presentation] Identification of a new dendritic cell progenitor with prominent plasmacytoid dendritic cell developmental potential. (2014)
  • Author(s): Onai N.
  • Organizer: The 9th International Symposium of the Institute Network.
  • Place of Presentation: Kobe
  • Year and Date: 2014-06-19 – 2014-06-20
  • Invited
• [Presentation] 単球由来樹状細胞樹状細胞による血球貪食と免疫制御 (2014)
  • Author(s): 小内 伸幸
  • Organizer: 第9回 先端血液学セミナー
  • Place of Presentation: 東京
  • Year and Date: 2014-06-07
  • Invited
• [Presentation] Plasmacytoid dendritic cell development. (2014)
  • Author(s): Onai N.
  • Organizer: The 22nd International
  • Place of Presentation: Osaka
  • Year and Date: 2014-06-02 – 2014-06-03
  • Invited
• [Presentation] Identification of M-CSFR- dendritic cell progenitors with prominent pDC developmental potential. : Revised load map for dendritic cell development. (2013)
  • Author(s): Onai N., et al
  • Organizer: Annual Meeting of The Japanese Society for Immunology
  • Place of Presentation: Makuhari Messe, Chiba
• [Presentation] Monocyte derived dendritic cells perform hemophagocytosis to fine-tune (2012)
  • Author(s): Onai N., et al.
  • Organizer: Annual Meeting of The Japanease Society for Immunology
  • Place of Presentation: Kobe
• [Presentation] Monocyte derived dendritic cells perform hemophagocytosis to fine-tune excessive immune responses. (2012)
  • Author(s): Onai,N., et al.
  • Organizer: The 20th International Symposium on Molecular Cell Biology of Macrophage.
  • Place of Presentation: Tokyo
  • Invited
• [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 トピックス
  • URL: http://www.tmd.ac.jp/mri/bre/index.html
• [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
• [Remarks] 東京医科歯科大学プレスリリース（免疫の司令塔、樹状細胞の源となる細胞を発見）
  • URL: http://www.tmd.ac.jp/press-release/20130426/index.html
• [Remarks] JSTプレスリリース（免疫の司令塔、樹状細胞の源となる細胞を発見）
  • URL: http://www.jst.go.jp/pr/announce/20130913/index.html
• [Remarks] 東京医科歯科大学プレスリリース（過剰な免疫反応を抑制する新たな樹状細胞のはたらきを発見）
  • URL: http://www.tmd.ac.jp/press-release/20130913/index.html
• [Remarks] JSTプレスリリース（過剰な免疫反応を抑制する新たな樹状細胞のはたらきを発見）
  • URL: http://www.jst.go.jp/pr/announce/20130913/index.html
• [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
• [Remarks] 東京医科歯科大学プレスリリース
  • URL: http://www.tmd.ac.jp/press-release/20130426/index.html