Control of hematopoiesis by dendritic cells

• Project/Area Number: 23591412
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Akita University
• Principal Investigator: SAWADA Kenichi 秋田大学, 医学(系)研究科(研究院), 教授 (90226069)
• Co-Investigator(Renkei-kenkyūsha): OHTEKI Toshiaki 東京医科歯科大学, 難治疾患研究所 先端分子医学研究部門, 教授 (50233200)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 造血幹・前駆細胞 / CD34+細胞 / 樹状細胞 / TLR / IL-10 / 二本鎖RNA / 一本鎖DNA / アポトーシス / マウスモデル / 血球貪食症候群 / ウイルス感染 / I型インターフェロン / CCR2 / 免疫制御 / 腫瘍壊死因子 / 阻害剤 / 造血幹細胞移植 / 移植片対宿主病 / CpG-ODN / 二重鎖RNA / ヒト造血幹細胞 / TLR3 / poly I:C / ROG-I / MDA5

Research Abstract

Dendritic cells (DC) produce various cytokines which may regulate the differentiation of hematopoietic stem cells (HSCs), however, the details of the relationship between dendritic cells and HSCs remains unclear. In this project, I revealed that the DC-stimulator TLR3 induces the prompt death of HSCs in vitro. Using mouse model, I also demonstrated that TLR9 stimulation or viral infection induces hemophagocytic syndrome, and that the phagocytes are monocyte-derived dendritic cells that produce IL-10. The produced IL-10 down-regulated hemophagocytosis, which suggests that hemophagocytosis is a novel immune suppressive mechanism to suppress an excessive immune response.

Research Products

• [Journal Article] MicroRNA-150 inhibits tumor invasion and metastasis by targeting the chemokine receptor CCR6, in advanced cutaneous T-cell lymphoma (2014)
  • Author(s): Ito M, Teshima K, Ikeda S, Kitadate A, Watanabe A, Nara M, Yamashita J, Ohshima K, Sawada K, Tagawa H
  • Journal Title: Blood Volume: 123(10) Pages: 1499-511
• [Journal Article] Monocyte-derived dendritic cells perform hemophagocytosis to fine-tune excessive immune responses (2013)
  • Author(s): Ohyagi H, Onai N, Sato T, Yotsumoto S, Liu J, Akiba H, Yagita H, Atarashi K, Honda K, Roers A, Müller W, Kurabayashi K, Hosoi-Amaike M, Takahashi N, Hirokawa M, Matsushima K, Sawada K, Ohteki T
  • Journal Title: Immunity Volume: 39(3) Pages: 584-98
  • NAID: 40020181881
• [Journal Article] Overall picture of an emerging neonatal infectious disease induced by a superantigenic exotoxin mainly produced by methicillin-resistant Staphylococcus aureus. (2013)
  • Author(s): Takahashi N, Imanishi K, Uchiyama T
  • Journal Title: Microbiol Immunol Volume: 57 Issue: 3 Pages: 737-745
  • DOI: 10.1016/j.immuni.2013.06.019
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A synthetic double-stranded RNA, poly I : C, induces a rapid apoptosis of human CD34(+) cells (2012)
  • Author(s): Liu J, Guo YM, Hirokawa M, Iwamoto K, Ubukawa K, Michishita Y, Fujishima N, Tagawa H, Takahashi N, Xiao W, Yamashita J, Ohteki T, Sawada K
  • Journal Title: Exp Hematol Volume: 40(4) Pages: 330-41
• [Journal Article] Enucleation of human erythroblasts involves non-muscle myosin IIB (2012)
  • Author(s): Ubukawa K, Guo YM, Takahashi M, Hirokawa M, Michishita Y, Nara M, Tagawa H, Takahashi N, Komatsuda A, Nunomura W, Takakuwa Y, Sawada K
  • Journal Title: Blood Volume: 119(4) Pages: 1036-44
• [Journal Article] A synthetic double-stranded RNA, poly I:C, induces a rapid apoptosis of human CD34+ cells (2012)
  • Author(s): Liu J
  • Journal Title: Experimental Hematology Volume: 40(4) Issue: 4 Pages: 330-341
  • DOI: 10.1016/j.exphem.2011.12.002
  • Peer Reviewed
• [Presentation] Enucleation of human erythroblasts is an actomyosin- dependent process following nuclear polarization (2011)
  • Author(s): Ubukawa K, Yong-Mei Guo, Hirokawa M, Michishita Y, Nara M, Tagawa H, Takahashi N , Komatsuda A , Nunomura W, Takakuwa Y, Sawada K
  • Organizer: 16th Congress of European Hematology Association
  • Place of Presentation: London
• [Presentation] RIG-I and MDA-5 signaling triggers apoptosis of human CD34+ cells in type 1 IFNs independent pathway (2011)
  • Author(s): Jiajia Liu, Y M Guo, Hirokawa M, Iwamoto K, Yamashita J, Ubukawa K, Michishita Y, Fujishima N, Tagawa H, Takahashi N, Ohteki T, Sawada K
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋
• [Remarks]
  • URL: http://www.imcr.gunma-u.ac.jp/gcoe/jpn/organization/members/sawada/index.html