Deletion of Notch1 Converts Pro-T Cells to Dendritic Cells and Promotes Thymic B Cells by Cell-Extrinsic and Cell-intrinsic Mechanisms
Deletion of Notch1 Converts Pro-T Cells to Dendritic Cells and Promotes Thymic B Cells by Cell-Extrinsic and Cell-intrinsic Mechanisms
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DOI：
10.1016/j.immuni.2008.10.016
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发表时间：
2009-01-16
期刊：
影响因子：
32.4
通讯作者：
Rodewald, Hans-Reimer
中科院分区：
文献类型：
--
作者：
Feyerabend, Thorsten B.;Terszowski, Grzegorz;Rodewald, Hans-Reimer
Notch 1信号传导是T细胞发育所必需的，并与胸腺中的命运决定有关。我们发现，Notch 1在祖T细胞（pro-T细胞）中的缺失揭示了它们向成为常规和浆细胞样树突状细胞的潜在发育潜力。此外，Notch 1在pro-T细胞中的缺失导致大量的胸腺B细胞，先前通过T细胞到B细胞的命运转换来解释。然而，单细胞基因分型表明，大多数这些胸腺B细胞通过细胞外源性途径由Notch 1充足细胞产生。然而，对于源自Notch 1缺失的pro-T细胞的胸腺B细胞亚群存在命运转换。在胸腺上皮中缺乏Notch配体δ样4（DII 4）的嵌合小鼠揭示了DII 4在T细胞发育中的重要作用。因此，Notch 1-DII 4信号传导通过抑制pro-T细胞中非T细胞谱系潜能来强化T细胞定型，并且正常Notch 1驱动的T细胞发育排斥胸腺中过量的B细胞。
Notch1 signaling is required for T cell development and has been implicated in fate decisions in the thymus. We showed that Notch1 deletion in progenitor T cells (pro-T cells) revealed their latent developmental potential toward becoming conventional and plasmacytoid dendritic cells. In addition, Notch1 deletion in pro-T cells resulted in large numbers of thymic B cells, previously explained by T-to-B cell fate conversion. Single-cell genotyping showed, however, that the majority of these thymic B cells arose from Notch1-sufficient cells by a cell-extrinsic pathway. Fate switching nevertheless exists for a subset of thymic B cells originating from Notch1 deleted pro-T cells. Chimeric mice lacking the Notch ligand delta-like 4 (DII4) in thymus epithelium revealed an essential role for DII4 in T cell development. Thus, Notch1-DII4 signaling fortifies T cell commitment by suppressing non-T cell lineage potential in pro-T cells, and normal Notch1-driven T cell development repels excessive B cells in the thymus.