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Publication : Cutting edge: thymic crosstalk regulates delta-like 4 expression on cortical epithelial cells.

First Author  Fiorini E Year  2008
Journal  J Immunol Volume  181
Issue  12 Pages  8199-203
PubMed ID  19050235 Mgi Jnum  J:142081
Mgi Id  MGI:3820369 Doi  10.4049/jimmunol.181.12.8199
Citation  Fiorini E, et al. (2008) Cutting edge: thymic crosstalk regulates delta-like 4 expression on cortical epithelial cells. J Immunol 181(12):8199-203
abstractText  Interactions between Notch1 receptors on lymphoid progenitors and Delta-like 4 (DL4) ligands on cortical thymic epithelial cells (cTEC) are essential for T cell lineage commitment, expansion, and maturation in the thymus. Using a novel mAb against DL4, we show that DL4 levels on cTEC are very high in the fetal and neonatal thymus when thymocyte expansion is maximal but decrease dramatically in the adult when steady-state homeostasis is attained. Analysis of mutant mouse strains where thymocyte development is blocked at different stages indicates that lymphostromal interactions ('thymus crosstalk') are required for DL4 down-regulation on cTEC. Reconstitution of thymocyte development in these mutant mice further suggests that maturation of thymocytes to the CD4(+)CD8(+) stage and concomitant expansion are needed to promote DL4 down-regulation on cTEC. Collectively, our data support a model where thymic crosstalk quantitatively regulates the rate of Notch1-dependent thymopoiesis by controlling DL4 expression levels on cTEC.
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