Regulation of hematopoiesis by dendritic cells

2007年，首席研究员由Y.Kawabata变更为T.Ohteki。我们进行了一项题为“树突状细胞（DC）对造血的调节"的研究。本研究旨在阐明与人造血干/祖细胞（CD 34+细胞）共培养的噬血DC的生理和病理作用，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）共刺激人CD 34+细胞产生巨核祖细胞（MP）和DC。CD 11 c + DCs能吞噬TNF-α损伤的MP，并诱导自体T细胞增殖。在噬血细胞综合征患者中也观察到CD 11 c + DCs对血细胞的吞噬。TNF-α诱导噬血细胞DC向红系分化，正如我们以前报道的。因此，本研究首次表明，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）后续研究发现巨核系和嗜血系噬血DC在刺激T淋巴细胞的方式上存在差异（ASH年会摘要，第1部分，108，第11期：488 a，2006年，3）非政府组织之间的DNA图谱分析，噬血DC和噬血DC的研究尚未完全完成，仍在继续。4）探讨树突状细胞（DCs）分泌IL-15诱导炎症性疾病的机制。我们表明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）。

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).