Regulation of hematopoiesis by dendritic cells

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)。

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).