Notch activation in thymic epithelial cells induces development of thymic microenvironments

Kyoko Masuda, Wilfred T.V. Germeraad, Rumi Satoh, Manami Itoi, Tomokatsu Ikawa, Nagahiro Minato, Yoshimoto Katsura, Willem van Ewijk, Hiroshi Kawamoto

研究成果: Article査読

17 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)1756-1767
ページ数12
ジャーナルMolecular Immunology
46
8-9
DOI
出版ステータスPublished - 05-2009
外部発表はい

All Science Journal Classification (ASJC) codes

  • 免疫学
  • 分子生物学

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