Control of hematopoiesis by dendritic cells

树突状细胞对造血的控制

• 批准号: 23591412
• 负责人: SAWADA Kenichi
• 金额: $ 3.41万
• 依托单位: Akita University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591412/
• 关键词: 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

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.

树突状细胞（Dendritic cells，DC）可产生多种细胞因子，调节造血干细胞（hematopoietic stem cells，HSC）的分化，但其与造血干细胞的关系尚不清楚。在这个项目中，我揭示了DC刺激因子TLR 3在体外诱导HSC的迅速死亡。使用小鼠模型，我还证明了TLR 9刺激或病毒感染诱导噬血细胞综合征，并且吞噬细胞是产生IL-10的单核细胞衍生的树突状细胞。产生的IL-10下调噬血细胞作用，这表明噬血细胞作用是一种新的免疫抑制机制，以抑制过度的免疫反应。

项目成果

Enucleation of human erythroblasts is an actomyosin- dependent process following nuclear polarization

人成红细胞的去核是核极化后肌动球蛋白依赖性过程

• 发表时间: 2011
• 作者: Ubukawa K;Yong-Mei Guo;Hirokawa M;Michishita Y;Nara M;Tagawa H;Takahashi N ;Komatsuda A ;Nunomura W;Takakuwa Y;Sawada K
• 通讯作者: Sawada K

Monocyte-Derived Dendritic Cells Perform Hemophagocytosis to Fine-Tune Excessive Immune Responses

• DOI: 10.1016/j.immuni.2013.06.019
• 发表时间: 2013-09-19
• 期刊: IMMUNITY
• 影响因子: 32.4
• 作者: Ohyagi, Hideaki;Onai, Nobuyuki;Ohteki, Toshiaki
• 通讯作者: Ohteki, Toshiaki

MicroRNA-150 inhibits tumor invasion and metastasis by targeting the chemokine receptor CCR6, in advanced cutaneous T-cell lymphoma

• DOI: 10.1182/blood-2013-09-527739
• 发表时间: 2014-03-06
• 期刊: BLOOD
• 影响因子: 20.3
• 作者: Ito, Mitsugu;Teshima, Kazuaki;Tagawa, Hiroyuki
• 通讯作者: Tagawa, Hiroyuki

A synthetic double-stranded RNA, poly I:C, induces a rapid apoptosis of human CD34+ cells

• DOI: 10.1016/j.exphem.2011.12.002
• 发表时间: 2012-04-01
• 期刊: EXPERIMENTAL HEMATOLOGY
• 影响因子: 2.6
• 作者: Liu, Jiajia;Guo, Yong-Mei;Sawada, Kenichi
• 通讯作者: Sawada, Kenichi

RIG-I and MDA-5 signaling triggers apoptosis of human CD34+ cells in type 1 IFNs independent pathway

RIG-I 和 MDA-5 信号传导在 1 型 IFN 独立途径中触发人 CD34+ 细胞凋亡

• 发表时间: 2011
• 作者: 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
• 通讯作者: Sawada K