Clonal type I interferon-producing and dendritic cell precursors are contained in both human lymphoid and myeloid progenitor populations

Clonal type I interferon-producing and dendritic cell precursors are contained in both human lymphoid and myeloid progenitor populations
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DOI:
10.1084/jem.20040809
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发表时间:
2004-12-06
影响因子:
15.3
通讯作者:
Manz, MG
Manz, MG
中科院分区:
医学1区
文献类型:
--
作者:
Chicha, L;Jarrossay, D;Manz, MG

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由于不同的细胞因子反应性、表面受体和转录因子表达,人CD 11 c(-)天然I型干扰素产生细胞(IPC)和CD 11 c(-)树突状细胞被认为分别通过淋巴和骨髓造血发育途径产生。为了直接检验这一假设,我们使用了一种体外试验,允许同时IPC,树突状细胞和B细胞的发展,我们测试了淋巴和骨髓定向造血祖细胞的发展能力。类造血祖细胞和普通骨髓祖细胞以及粒细胞/巨噬细胞祖细胞能够发育成功能性IPC(表达被认为与淋巴谱系发育相关的基因转录物)和树突状细胞。然而,两个群体的克隆祖细胞在髓系定向祖细胞中的频率约为5倍。因此,在人类和小鼠中,天然IPC和树突状细胞发育与髓样分化强烈分离。这与天然的I型干扰素产生细胞和树突状细胞在先天免疫中的活性相吻合,先天免疫是细胞免疫系统进化的老分支。
Because of different cytokine responsiveness, surface receptor, and transcription factor expression, human CD11c(-) natural type I interferon-producing cells (IPCs) and CD11c(-) dendritic cells were thought to derive through lymphoid and myeloid hematopoietic developmental pathways, respectively. To directly test this hypothesis, we used an in vitro assay allowing simultaneous IPC, dendritic cell, and B cell development and we tested lymphoid and myeloid committed hematopoietic progenitor cells for their developmental capacity. Lymphoid and common myeloid and granulocyte/macrophage progenitors were capable of developing into both functional IPCs, expressing gene transcripts thought to be associated with lymphoid lineage development, and into dendritic cells. However, clonal progenitors for both populations were about fivefold more frequent within myeloid committed progenitor cells. Thus, in humans as in mice, natural IPC and dendritic cell development robustly segregates with myeloid differentiation. This would fit with natural interferon type I-producing cell and dendritic cell activity in innate immunity, the evolutionary older arm of the cellular immune system.