Regulation of T lymphopoiesis by Notch1 and Lunatic fringe-mediated competition for intrathymic niches.
Nat Immunol
; 7(6): 634-43, 2006 Jun.
Article
em En
| MEDLINE
| ID: mdl-16699526
ABSTRACT
Notch1 activation regulates T lineage commitment and early T cell development. Fringe glycosyltransferases alter the sensitivity of Notch receptors to Delta-like versus Jagged Notch ligands, but their functions in T lymphopoiesis have not been defined. Here we show that developmental stage-specific expression of the glycosyltransferase lunatic fringe (Lfng) is required for coordination of the access of T cell progenitors to intrathymic niches that support Notch1-dependent phases of T cell development. Lfng-null progenitors generated few thymocytes in competitive assays, whereas Lfng overexpression converted thymocytes into 'supercompetitors' with enhanced binding of Delta-like ligands and blocked T lymphopoiesis from normal progenitors. We suggest that the ability of Lfng and Notch1 to control progenitor competition for limiting cortical niches is an important mechanism for the homeostatic regulation of thymus size.
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Base de dados:
MEDLINE
Assunto principal:
Timo
/
Linfócitos T
/
Glicosiltransferases
/
Linfopoese
/
Receptor Notch1
Limite:
Animals
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article