Regulation of hematopoiesis by dendritic cells

2007年，首席研究员从川端康成（Y.Kawabata）改为大木（T.Ohteki）。我们进行了一项名为“树突状细胞（DC）对造血的调节”的研究。我们计划本研究阐明噬血DC与人造血干细胞/祖细胞（CD34+细胞）造血祖细胞共同发育的生理和病理作用，得到以下结果：1)血小板生成素（TPO）和肿瘤坏死因子-α (TNF-α)共同刺激人CD34+细胞产生巨核细胞祖细胞（MPs）和DC。发现CD11c+ dc可通过TNF-α吞噬受损的MPs，并诱导自身t细胞增殖。在噬血细胞综合征患者中也观察到CD11c+ DCs对血细胞的吞噬。TNF-α在红细胞谱系分化中诱导噬血细胞DC，正如我们之前报道的那样。因此，本研究首次提出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)随后的研究表明巨核细胞和中性粒细胞的噬血细胞DC在刺激T淋巴细胞的方式上是不同的（ASH年会摘要，第1部分，108,Issue 11:488a, 2006，准备提交）。3)非噬血DC与噬血DC的DNA谱分析尚未完全完成，仍在继续进行中。4)探讨树突状细胞产生的IL-15诱导炎性疾病的机制。我们发现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).