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  • Review Article
  • Published:

Intestinal lymphatic vasculature: structure, mechanisms and functions

Nature Reviews Gastroenterology & Hepatology volume 14, pages 510–526 (2017)Cite this article

Subjects

Key Points

  • Intestinal lymphatic vessels are critical for fat absorption and gut immunosurveillance

  • Some of the molecular mechanisms of intestinal lymphatic development and maintenance are distinct from other lymphatic vessel beds

  • Intestinal lymphatic dysfunction is likely a contributing factor in intestinal pathologies such as IBD

  • Modulating intestinal lymphatic patterning and/or function might provide novel therapies for gastrointestinal tract diseases

Abstract

The mammalian intestine is richly supplied with lymphatic vasculature, which has functions ranging from maintenance of interstitial fluid balance to transport of antigens, antigen-presenting cells, dietary lipids and fat-soluble vitamins. In this Review, we provide in-depth information concerning the organization and structure of intestinal lymphatics, the current view of their developmental origins, as well as molecular mechanisms of intestinal lymphatic patterning and maintenance. We will also discuss physiological aspects of intestinal lymph flow regulation and the known and emerging roles of intestinal lymphatic vessels in human diseases, such as IBD, infection and cancer.

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Figure 1: Intestinal lymphatic vessel organization.
Figure 2: Lacteal length relative to the villus length along the small intestine.
Figure 3: Molecular mechanisms of intestinal lymphatic development and remodelling.
Figure 4: Intestinal lacteal absorption and immune cell trafficking.
Figure 5: Intestinal lymph draining pattern and contents.
Figure 6: Schematic depiction of the role of intestinal lymphatic vessel dysfunction in gut pathology.

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Acknowledgements

We apologize to many colleagues whose contributions were not discussed because of space limitations. We thank A. Sabine (University of Lausanne, Switzerland) for the confocal image of mesenteric lymphatics and both A. Sabine and D. Velin (Lausanne University Hospital, Switzerland) for critical reading of the manuscript. The work in the author's laboratory is supported by the Swiss National Science Foundation (CRSII3-141811, 31003A-156266 and CR32I3_166326), MEDIC, Gebert Rüf, Novartis and Swiss Bridge foundations, TheraLymph ERA-NET E-Rare Research Programme (FNS 31ER30_160674), The Commission for Technology and Innovation, Fondazione San Salvatore, Swiss Cancer League (KLS 3406-02-2014), and the People Programme (Marie Curie Actions) of the EU's Seventh Framework Programme FP7/2007 to 2013 under REA grant agreement 317250.

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Authors and Affiliations

  1. Department of Fundamental Oncology, Ludwig Institute for Cancer Research and Institute of Pathology, Centre Hospitalier Universitaire Vaudois and University of Lausanne (UNIL), Chemin des Boveresses 155, Epalinges, Switzerland

    Jeremiah Bernier-Latmani & Tatiana V. Petrova

  2. Swiss Institute for Experimental Cancer Research, School of Life Sciences, Swiss Federal Institute of Technology Lausanne, Route Cantonale 1015, Lausanne, Switzerland

    Tatiana V. Petrova

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  1. Jeremiah Bernier-Latmani
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  2. Tatiana V. Petrova
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Both authors contributed equally to all aspects of this manuscript.

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Correspondence to Tatiana V. Petrova.

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Competing interests

T.V.P. received a research grant from Hoffman-La Roche to investigate angiogenesis inhibitors.

Supplementary information

Supplementary information S1 (table)

Intestinal lymphatic vascular defects in genetic mouse models (PDF 271 kb)

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Glossary

Lacteals

Central lymphatic capillaries in small intestinal villi.

Button junctions

Discontinuous specialized cell–cell junctions found in normal mature lymphatic capillaries that facilitate the passage of interstitial components and immune cells into the lymphatic vessel lumen while maintaining vessel integrity

Zipper junctions

Continuous and relatively impermeable junctions found in normal developing and mature lymphatic collecting vessels.

Lymphatic valves

Intraluminal bi-leaflet structures, covered on both sides with endothelial cells; valves are present in lymphatic collecting vessels and they ensure unidirectional lymph flow towards blood circulation.

Filopodia

Fine cytoplasmic, actin-rich cellular extensions usually observed in migrating cells, most often found in migrating blood or lymphatic endothelial cells.

Chylous ascites

Accumulation of intestinal lymph in the abdomen, which appears white because of the presence of chylomicrons.

Lymphangiectasia

Pathological dilation and malfunction of intestinal lymphatic vessels.

Chylomicrons

Largest lipoprotein particle secreted by enterocytes after dietary long-chain fatty acid absorption; chylomicrons can also transport cholesterol, fat-soluble vitamins and lipopolysaccharide from the intestinal microbiota.

Chyle

Fat-droplet rich, milky-white lymph draining from the intestine.

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Bernier-Latmani, J., Petrova, T. Intestinal lymphatic vasculature: structure, mechanisms and functions. Nat Rev Gastroenterol Hepatol 14, 510–526 (2017). https://doi.org/10.1038/nrgastro.2017.79

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