DLL4 promotes continuous adult intestinal lacteal regeneration and dietary fat transport.

Détails

Ressource 1Télécharger: JCI82045.pdf (8496.81 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_BA1CB6D590A9
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
DLL4 promotes continuous adult intestinal lacteal regeneration and dietary fat transport.
Périodique
Journal of Clinical Investigation
Auteur(s)
Bernier-Latmani J., Cisarovsky C., Demir C.S., Bruand M., Jaquet M., Davanture S., Ragusa S., Siegert S., Dormond O., Benedito R., Radtke F., Luther S.A., Petrova T.V.
ISSN
1558-8238 (Electronic)
ISSN-L
0021-9738
Statut éditorial
Publié
Date de publication
2015
Peer-reviewed
Oui
Volume
2015
Pages
4572-4586
Langue
anglais
Notes
Publication types: Journal ArticlePublication Status: epublish
Résumé
The small intestine is a dynamic and complex organ that is characterized by constant epithelium turnover and crosstalk among various cell types and the microbiota. Lymphatic capillaries of the small intestine, called lacteals, play key roles in dietary fat absorption and the gut immune response; however, little is known about the molecular regulation of lacteal function. Here, we performed a high-resolution analysis of the small intestinal stroma and determined that lacteals reside in a permanent regenerative, proliferative state that is distinct from embryonic lymphangiogenesis or quiescent lymphatic vessels observed in other tissues. We further demonstrated that this continuous regeneration process is mediated by Notch signaling and that the expression of the Notch ligand delta-like 4 (DLL4) in lacteals requires activation of VEGFR3 and VEGFR2. Moreover, genetic inactivation of Dll4 in lymphatic endothelial cells led to lacteal regression and impaired dietary fat uptake. We propose that such a slow lymphatic regeneration mode is necessary to match a unique need of intestinal lymphatic vessels for both continuous maintenance, due to the constant exposure to dietary fat and mechanical strain, and efficient uptake of fat and immune cells. Our work reveals how lymphatic vessel responses are shaped by tissue specialization and uncover a role for continuous DLL4 signaling in the function of adult lymphatic vasculature.
Pubmed
Web of science
Open Access
Oui
Création de la notice
03/01/2016 16:25
Dernière modification de la notice
20/08/2019 15:28
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