ArticleThe Journal of clinical investigation2015
DLL4 promotes continuous adult intestinal lacteal regeneration and dietary fat transport.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers.
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Who cites it
114 citing papers in PubMed, 182 citations in OpenAlex.
- Intestinal fructose catabolism promotes obesity and insulin resistance via ileal lacteal remodeling.Science advances · 2026Article
- Lymphatic Endothelial Cells in Health and Disease.MedComm · 2026Review
- Eosinophils promote a second wave of postnatal smooth muscle differentiation in intestinal villi.The Journal of cell biology · 2026Article
- Dysfunctional adipose tissue-lymphatic crosstalk in obesity.Nature reviews. Endocrinology · 2026Review
- GPR182 is a lipoprotein receptor for dietary fat absorption.The Journal of clinical investigation · 2026Article
- Interventions and platforms that direct lymphangiogenesis to restore physiological homeostasis and enhance immunoregulation.NPJ Regenerative medicine · 2026Review
- IFNγ-dependent metabolic reprogramming restrains an immature, pro-metastatic lymphatic state in melanoma.Cancer cell · 2026Article
- Insights into KIF11 pathogenesis in microcephaly-lymphedema-chorioretinopathy syndrome from a lymphatic perspective.JCI insight · 2026Article
- Lung Lymphatics in Edema, Inflammation, and Thrombosis.Arteriosclerosis, thrombosis, and vascular biology · 2025Review
- APOA1 binding protein promotes lymphatic cell fate and lymphangiogenesis by relieving caveolae-mediated inhibition of VEGFR3 signaling.Nature communications · 2025Article
- Intestinal lymphatic vasculature is functionally adapted to different drainage regions and is altered by helminth infection.The Journal of experimental medicine · 2025Article
- From defense to disease: the multifaceted role of lymphatics during infection.Journal of immunology (Baltimore, Md. : 1950) · 2025Review
- Defective lymphatic vasculature in obesity.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025Review
- DHHC5 regulates lacteal function and intestinal lipid absorption by maintaining VEGFR2 localization in lipid rafts.Life metabolism · 2025Article
- TIE1-dependent lymphatic vascular remodeling is mediated by its second tyrosine kinase domain.Development (Cambridge, England) · 2025Article
- Article
- Lymphatic mysteries unzipped.Nature cardiovascular research · 2025Article
- Transport functions of intestinal lymphatic vessels.Nature reviews. Gastroenterology & hepatology · 2025Review
- The role of transcytosis in the blood-retina barrier: from pathophysiological functions to drug delivery.Frontiers in pharmacology · 2025Review
- Electroacupuncture Combined with Press Needles Alleviates Simple Obesity via VEGF-C/VEGFR-3/PI3K/AKT Signaling Pathway.Obesity facts · 2025Article
54 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.