Expression pattern of Notch1, 2 and 3 and Jagged1 and 2 in lymphoid and stromal thymus components: distinct ligand-receptor interactions in intrathymic T cell development
Expression pattern of Notch1, 2 and 3 and Jagged1 and 2 in lymphoid and stromal thymus components: distinct ligand-receptor interactions in intrathymic T cell development
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DOI：
10.1093/intimm/11.7.1017
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发表时间：
1999-07-01
影响因子：
4.4
通讯作者：
Screpanti, I
中科院分区：
文献类型：
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作者：
Felli, MP;Maroder, M;Screpanti, I
Notch1或其突变体在胸腺细胞分化和T细胞肿瘤发生中的作用提出了一个问题，即Notch家族的不同成员如何影响T细胞发育的不同步骤以及Notch配体在胸腺中所起的作用。我们在这里报告了不同的Notch受体-配体伙伴关系可能在胸腺内发生，因为我们观察到Notch1，2和3受体，它们的配体Jagged1和2，以及下游细胞内效应分子HES-1和HES-1以及HES-5，取决于个体发育阶段和胸腺细胞群。事实上，虽然Jagged2在基质细胞和胸腺细胞中都有表达，但Jagged1的表达仅限于基质细胞。此外，在不同的年龄相关胸腺细胞亚群中观察到Notch3与Notch1的不同分布。最后，Notch3在胸腺细胞通过与表达同源Jagged1和2配体的胸腺上皮细胞相互作用而诱导分化后，优先上调，这表明，除了Notch1，Notch3还可能参与胸腺细胞发育的不同阶段。我们的结果表明，Notch信号通路参与了T细胞发育阶段的复杂相互作用，这是由于Notch受体家族成员及其同源配体在不同的胸腺细胞亚群中的异质性和特异性表达的结果。
The suggested role of Notch1 or its mutants in thymocyte differentiation and T cell tumorigenesis raises the question of how the different members of the Notch family influence distinct steps in T cell development and the role played by Notch ligands in the thymus, We report here that different Notch receptor-ligand partnerships may occur inside the thymus, as we observed differential expression of Notch1, 2 and 3 receptors, their ligands Jagged1 and 2, and downstream intracellular effecters hairy and Enhancer of Spill homolog 1 (HES-1) and hairy and Enhancer of Split homolog 5 (HES-5), depending on ontogenetic stage and thymic cell populations. Indeed, while Jagged2 is expressed in both stromal cells and thymocytes, Jagged1 expression is restricted to stromal cells. Moreover, a differential distribution of Notch3, with respect to Notch1, was observed in distinct age-related thymocyte subsets. Finally, Notch3 was preferentially up-regulated in thymocytes, following the induction of their differentiation by interaction with thymic epithelial cells expressing the cognate Jagged1 and 2 ligands, suggesting that, besides Notch1, Notch3 may also be involved in distinct steps of thymocyte development. Our results suggest that the Notch signaling pathway is involved in a complex interplay of T cell developmental stages, as a consequence of the heterogeneity and specific expression of members of the Notch receptor family and their cognate ligands, in distinct thymic cell compartments.