DL4-mediated Notch signaling is required for the development of fetal αβ and γδ T cells.
Details
Serval ID
serval:BIB_4AF30449CEB7
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
DL4-mediated Notch signaling is required for the development of fetal αβ and γδ T cells.
Journal
European Journal of Immunology
ISSN
1521-4141 (Electronic)
ISSN-L
0014-2980
Publication state
Published
Issued date
2013
Volume
43
Number
11
Pages
2845-2853
Language
english
Abstract
T-cell development depends upon interactions between thymocytes and thymic epithelial cells (TECs). The engagement of delta-like 4 (DL4) on TECs by Notch1 expressed by blood-borne BM-derived precursors is essential for T-cell commitment in the adult thymus. In contrast to the adult, the earliest T-cell progenitors in the embryo originate in the fetal liver and migrate to the nonvascularized fetal thymus via chemokine signals. Within the fetal thymus, some T-cell precursors undergo programmed TCRγ and TCRδ rearrangement and selection, giving rise to unique γδ T cells. Despite these fundamental differences between fetal and adult T-cell lymphopoiesis, we show here that DL4-mediated Notch signaling is essential for the development of both αβ and γδ T-cell lineages in the embryo. Deletion of the DL4 gene in fetal TECs results in an early block in αβ T-cell development and a dramatic reduction of all γδ T-cell subsets in the fetal thymus. In contrast to the adult, no dramatic deviation of T-cell precursors to alternative fates was observed in the fetal thymus in the absence of Notch signaling. Taken together, our data reveal a common requirement for DL4-mediated Notch signaling in fetal and adult thymopoiesis.
Keywords
Delta-like 4, Fetal T-cell development, FoxN1Cre, Thymic epithelial cells
Pubmed
Web of science
Open Access
Yes
Create date
14/01/2014 14:43
Last modification date
20/08/2019 13:58