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EMBO Rep. 2019 Apr;20(4). pii: e46927. doi: 10.15252/embr.201846927. Epub 2019 Feb 19.

Gut microbiota regulates lacteal integrity by inducing VEGF-C in intestinal villus macrophages.

Author information

1
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
2
Graduate School of Nanoscience and Technology, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
3
Center for Vascular Research, Institute for Basic Science, Daejeon, Korea.
4
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
5
Academy of Immunology and Microbiology, Institute for Basic Science, Pohang, Korea.
6
Translational Cancer Biology Program and Wihuri Research Institute, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
7
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea gykoh@kaist.ac.kr jhsong0907@gmail.com.
8
Center for Vascular Research, Institute for Basic Science, Daejeon, Korea gykoh@kaist.ac.kr jhsong0907@gmail.com.

Abstract

A lacteal is a blunt-ended, long, tube-like lymphatic vessel located in the center of each intestinal villus that provides a unique route for drainage of absorbed lipids from the small intestine. However, key regulators for maintaining lacteal integrity are poorly understood. Here, we explore whether and how the gut microbiota regulates lacteal integrity. Germ depletion by antibiotic treatment triggers lacteal regression during adulthood and delays lacteal maturation during the postnatal period. In accordance with compromised lipid absorption, the button-like junction between lymphatic endothelial cells, which is ultrastructurally open to permit free entry of dietary lipids into lacteals, is significantly reduced in lacteals of germ-depleted mice. Lacteal defects are also found in germ-free mice, but conventionalization of germ-free mice leads to normalization of lacteals. Mechanistically, VEGF-C secreted from villus macrophages upon MyD88-dependent recognition of microbes and their products is a main factor in lacteal integrity. Collectively, we conclude that the gut microbiota is a crucial regulator for lacteal integrity by endowing its unique microenvironment and regulating villus macrophages in small intestine.

KEYWORDS:

VEGF‐C; intestinal lymphatic vasculature; lacteal; macrophage; microbiota

PMID:
30783017
PMCID:
PMC6446200
[Available on 2020-04-01]
DOI:
10.15252/embr.201846927

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