Regulation of hematopoiesis by dendritic cells

树突状细胞对造血的调节

• 批准号: 17590978
• 负责人: OHTEKI Toshiaki
• 金额: $ 2.24万
• 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: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590978/
• 关键词: CD34; Erythroblast; Megakaryocyte; Dendritic cells; CD11c; Interleukin-15; hemophagocytic syndrome; CD11c; 血球貧食症候群; 巨核球系前駆細胞; TNF-α; 貪食; 免疫寛容

The head investigator has been changed from Y.Kawabata to T.Ohteki at 2007. We conducted a study entitled "Regulation of hematopoiesis by dendritic cells (DC)". We planned this study to clarify the physiological and pathological role of hemophagocytosing DC co-developed with hematopoietic progenitors from human hematopoietic stem/progenitor cells (CD34+ cells) and obtained the following results :1) The costimulation of thrombopoietin (TPO) and tumor necrosis factor-α (TNF-α) generated megakaryocytic progenitors (MPs) and DC together from human CD34+ cells. CD11c+ DCs were found to engulf damaged MPs by TNF-α and to induce autologous T-cell proliferation. An engulfment of blood cells by CD11c+ DCs was also observed in patients with hemophagocytic syndrome. TNF-α induces hemophagocytic DC in erythroid lineage differentiation, as we reported previously. Thus, this study, for the first time, suggested that DC generated under hematopoietic and inflammatory stimuli are involved in hematopoiesis and the subsequent immune responses (Blood 2006;107:1366).2) Subsequent study revealed that the nature of hemophagocytic DC is different between megakaryocytic and neutrophilic lineage in the way for stimulating T lymphocytes (ASH Annual Meeting Abstracts, Part 1, 108, Issue 11:488a, 2006, in preparation for submitting).3) The analysis of DNA profiling between non-hemophagocytosing DC and hemophagocytosing DC has not been completely accomplished and been being continued.4) The induction mechanism of inflammatory diseases by IL-15 produced from dendritic cells (DCs) was investigated. We showed that IL-15 is requisite for the induction of granuloma formation and endotoxin-shock (J Exp Med 2006;203:2329).

2007年，首席调查员从Y.Kawabata改为T.Ohteki。我们进行了一项题为“树突状细胞(DC)对造血的调控”的研究。本研究旨在阐明与人造血干/祖细胞共培养的吞血树突状细胞的生理和病理作用，并获得以下结果：1)血小板生成素和肿瘤坏死因子-α共刺激人CD34+细胞产生巨核系祖细胞和树突状细胞。CD11c+DC可吞噬经肿瘤坏死因子-α损伤的MPS，并诱导自体T细胞增殖。吞噬血细胞综合征患者CD11c+DC吞噬血细胞。正如我们先前报道的那样，肿瘤坏死因子-α诱导噬血细胞DC向红系分化。因此，这项研究首次表明，在造血和炎症刺激下产生的树突状细胞参与了造血和随后的免疫反应(血液2006；107：1366)2)后续研究发现巨核细胞DC和中性粒细胞DC在刺激T淋巴细胞的方式上具有不同的性质(ASH年会摘要，第1部分，108期，2006年第11期：488a，准备提交)。3)对非吞血性DC和嗜血性DC之间的DNA图谱分析尚未完全完成，并一直在继续。4)树突状细胞(DC)产生的IL-15诱导炎症疾病的机制。我们证明了IL-15是诱导肉芽肿形成和内毒素休克所必需的(J Exp Med 2006；203：2329)。

项目成果

Successful autologous peripheral blood stem cell transplantation using thiotepa in a patient with systemic sclerosis and cardiac involvement.

使用塞替派对患有系统性硬化症和心脏受累的患者成功进行自体外周血干细胞移植。

• 发表时间: 2006
• 期刊: Tohoku J Exp Med 209(1)
• 作者: Komatsuda A;Ohtani H;Wakui H;Chyzh KA;Hatakeyama T;Iwamoto K;Maki N;Kimura T;Hitomi J;Sawada K
• 通讯作者: Sawada K

赤芽球癆の病態と治療(編集 : 専門医のための薬物療法 Q＆A 血液)(押味和夫、小松則夫、長澤俊郎)

红细胞发育不全的病理学和治疗（编辑：专家的药物治疗问答血液）（Kazuo Oshimi、Norio Komatsu、Toshiro Nagasawa）

• 作者: 澤田賢一;廣川誠
• 通讯作者: 廣川誠

幹細胞・造血因子(編集 : 高齢者の血液疾患)(森真由美)

干细胞和造血因子（编辑：老年人血液疾病）（森真由美）

• 发表时间: 2005
• 作者: Tomonari A;Takahashi S;et al.;澤田賢一
• 通讯作者: 澤田賢一

Development of systemic λ-light chain amyloidosis in a patient with γ-heavy chain deposition disease during long-term follow-up

• DOI: 10.1093/ndt/gfh545
• 发表时间: 2005-02-01
• 期刊: NEPHROLOGY DIALYSIS TRANSPLANTATION
• 影响因子: 6.1
• 作者: Komatsuda, A;Maki, N;Sawada, K
• 通讯作者: Sawada, K

赤芽球癆診療の参照ガイド-PRCAの診療基準と診療の参照ガイド作成のためのワーキンググループ-

成红细胞再生障碍性治疗参考指南 - 制定 PRCA 治疗标准和治疗参考指南工作组 -

• 发表时间: 2006
• 期刊: 臨床血液 47 (4)
• 作者: 澤田賢一;浦部晶夫;中尾眞二;別所正美;唐沢正光;石田陽治;小松則夫;増田道彦;廣川誠;茂木睦仁;小峰光博
• 通讯作者: 小峰光博