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

Details

Ressource 1Download: JCI82045.pdf (8496.81 [Ko])
State: Public
Version: Final published version
Serval ID
serval:BIB_BA1CB6D590A9
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
DLL4 promotes continuous adult intestinal lacteal regeneration and dietary fat transport.
Journal
Journal of Clinical Investigation
Author(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
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
2015
Pages
4572-4586
Language
english
Notes
Publication types: Journal ArticlePublication Status: epublish
Abstract
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
Yes
Create date
03/01/2016 16:25
Last modification date
20/08/2019 15:28
Usage data