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，首席研究员从Y.Kawabata变更为T.Ohteki。我们进行了一项题为“树突状细胞（DC）的造血调节”的研究，旨在阐明噬血细胞DC的生理和病理作用。用人类造血干/祖细胞（CD34+细胞）的造血祖细胞开发并获得以下结果：1）血小板生成素 (TPO) 和肿瘤坏死因子-α (TNF-α) 的共刺激从人 CD34+ 细胞中产生巨核细胞祖细胞 (MP) 和 DC，发现 TNF-α 吞噬受损的 MP 并诱导自体 T 细胞。在噬血细胞综合征患者中也观察到 CD11c+ DC 吞噬血细胞。正如我们之前报道的，这项研究首次表明，在造血和炎症刺激下产生的 DC 参与造血和随后的免疫反应（Blood 2006；107：1366）。 2）后续研究表明，巨核细胞系和中性粒细胞系的噬血细胞DC在刺激T的方式上存在差异。 （ASH 年会摘要，第 1 部分，108，第 11：488a，2006 年，准备提交）。3）非噬血 DC 和噬血 DC 之间的 DNA 谱分析尚未完全完成，仍在继续。 4)研究了树突状细胞(DC)产生的IL-15诱导炎症疾病的机制。我们发现IL-15是一种炎症性疾病。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

Acquired aplastic anemia and pure red cell aplasia.

获得性再生障碍性贫血和纯红细胞再生障碍性贫血。

• 发表时间: 2005
• 作者: Konuma T;Takahashi S;et al.;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

Increased serum levels of S100A12 in patients with MPO-ANCA-associated glomerulonephritis.

• DOI: 10.5414/cnp66315
• 发表时间: 2006-11
• 期刊: Clinical nephrology
• 影响因子: 1.1
• 作者: A. Komatsuda;H. Ohtani;H. Wakui;K. Chyzh;T. Hatakeyama;K. Iwamoto;N. Maki;T. Kimura;J. Hitomi;K. Sawada

Development of lupus nephritis in a patient with human T-cell lymphotropic virus type I-associated myelopathy.

患有人类 T 细胞嗜淋巴细胞病毒 I 型相关脊髓病的患者出现狼疮肾炎。

• 发表时间: 2005
• 期刊: Am J Kidney Dis 46 (2)
• 作者: Wakui H;Masai R;Okuyama S;Ohtani H;Komatsuda A;Toyoshima I;Watanabe S;Sawada K
• 通讯作者: Sawada K

Oligoclonal T cell expansion in blood but not in the thymus from a patient with thymoma-associated pure red cell aplasia.

胸腺瘤相关纯红细胞再生障碍性贫血患者的血液中寡克隆 T 细胞扩增，但胸腺中未扩增。

• 发表时间: 2006
• 期刊: Haematologica 91(12 Suppl)
• 作者: Fujishima N;Hirokawa M;Fujishima M;Wada C;Toyoshima I;Watanabe S;Sawada K
• 通讯作者: Sawada K