Notch1 deficiency dissociates the intrathymic development of dendritic cells and T cells.
Notch1 deficiency dissociates the intrathymic development of dendritic cells and T cells.
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DOI：
10.1084/jem.191.7.1085
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发表时间：
2000-04-03
影响因子：
15.3
通讯作者：
MacDonald, H R
中科院分区：
文献类型：
--
作者：
Radtke, F;Ferrero, I;Wilson, A;Lees, R;Aguet, M;MacDonald, H R
胸腺树突状细胞(DC)是骨髓来源的细胞的一个离散亚群，其功能是介导自身反应性胸腺细胞的阴性选择。胸腺树突状细胞的发育起源仍存在争议。尽管细胞移植研究支持T细胞和胸腺DC由同一胸腺内多潜能前体细胞发展而来的模型，但这两种类型的细胞仍有可能是从独立的胸腺内前体细胞发展而来的。Noch蛋白是参与细胞命运调控的细胞表面受体。我们最近报道了可诱导Notch1缺陷小鼠的T细胞发育在T细胞谱系标志物表达之前的早期阶段就严重受损。为了研究胸腺树突状细胞的发育是否也依赖于Notch1，我们构建了混合BM嵌合小鼠。我们在这里报道，在这种竞争的情况下，胸腺DC从Notch1−/−BM前体细胞发育是绝对正常的(就绝对数量和表型而言)，尽管Notch1−/−T细胞缺失。此外，我们发现外周树突状细胞和朗格汉斯细胞也不受Notch1缺乏的影响。我们的结果表明，DC的发育完全不依赖Notch1的功能，并强烈提示胸腺内T细胞和DC前体之间存在分离。
Thymic dendritic cells (DCs) form a discrete subset of bone marrow (BM)-derived cells, the function of which is to mediate negative selection of autoreactive thymocytes. The developmental origin of thymic DCs remains controversial. Although cell transfer studies support a model in which T cells and thymic DCs develop from the same intrathymic pluripotential precursor, it remains possible that these two types of cells develop from independent intrathymic precursors. Notch proteins are cell surface receptors involved in the regulation of cell fate specification. We have recently reported that T cell development in inducible Notch1-deficient mice is severely impaired at an early stage, before the expression of T cell lineage markers. To investigate whether development of thymic DCs also depends on Notch1, we have constructed mixed BM chimeric mice. We report here that thymic DC development from Notch1−/− BM precursors is absolutely normal (in terms of absolute number and phenotype) in this competitive situation, despite the absence of Notch1−/− T cells. Furthermore, we find that peripheral DCs and Langerhans cells are also not affected by Notch1 deficiency. Our results demonstrate that the development of DCs is totally independent of Notch1 function, and strongly suggest a dissociation between intrathymic T cell and DC precursors.