Notch activation in thymic epithelial cells induces development of thymic microenvironments
Notch activation in thymic epithelial cells induces development of thymic microenvironments
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DOI：
10.1016/j.molimm.2009.01.015
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发表时间：
2009-05-01
影响因子：
3.6
通讯作者：
Kawamoto, Hiroshi
中科院分区：
文献类型：
--
作者：
Masuda, Kyoko;Germeraad, Wilfred T. V.;Kawamoto, Hiroshi
胸腺微环境的发育和维持依赖于来自发育中胸腺细胞的持续串扰信号。然而，胸腺上皮细胞（TECs）淋巴依赖性发育的初始阶段的分子基础仍然不清楚。在这里，我们表明，类似于正常的胸腺细胞，开发B细胞被迫表达Notch配体Delta-like-1（DLL 1）有效地诱导非极化，三维（3D）网状结构的皮质TEC在胎儿胸腺器官培养。此外，DLL 1过表达的B细胞诱导发育良好的不同髓质。这种髓质也出现在用过表达DLL 1的Rag 2（-/-）胸腺细胞重建的叶中。因此，我们目前的研究结果强烈表明，Notch信号从胸腺细胞TEC诱导TEC的发展在胸腺器官发生的早期阶段。本方法使用非T细胞系细胞在体外构建胸腺环境，也可以提供一种新的工具，胸腺再生和T细胞的生产免疫功能低下的个人。(C)2009爱思唯尔有限公司保留所有权利。
The development and maintenance of thymic microenvironments depends on sustained crosstalk signals derived from developing thymocytes. However, the molecular basis for the initial phase in the lymphoid dependent development of thymic epithelial cells (TECs) remains unclear. Here we show that similarly to regular thymocytes, developing B cells enforced to express the Notch ligand Delta-like-1 (DLL1) efficiently induce the non-polarized, three-dimensional (3D) meshwork architecture of cortical TECs in fetal thymic organ culture. Moreover, the DLL1-overexpressing B cells induce well-developed distinct medullae. Such medullae also arose in lobes reconstituted with Rag2(-/-) thymocytes overexpressing DLL1. Our present findings thus strongly suggest that Notch signaling from thymocytes to TECs induces TEC development at an early phase of thymic organogenesis. The present approach using non-T lineage cells for the in vitro construction of thymic environments may also provide a novel tool for thymus regeneration and T cell production in immunocompromised individuals. (C) 2009 Elsevier Ltd. All rights reserved.