Gut microbiota regulates lacteal integrity by inducing VEGF-C in intestinal villus macrophages.
Age Factors
Animals
Biological Transport
Biomarkers
CX3C Chemokine Receptor 1
/ metabolism
Fluorescent Antibody Technique
Gastrointestinal Microbiome
Intestinal Absorption
Intestinal Mucosa
/ cytology
Lipid Metabolism
Macrophages
/ metabolism
Mice
Microvessels
/ metabolism
Myeloid Differentiation Factor 88
/ metabolism
Signal Transduction
Vascular Endothelial Growth Factor C
/ biosynthesis
VEGF‐C
intestinal lymphatic vasculature
lacteal
macrophage
microbiota
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
04 2019
04 2019
Historique:
received:
17
08
2018
revised:
11
01
2019
accepted:
21
01
2019
pubmed:
21
2
2019
medline:
1
5
2020
entrez:
21
2
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30783017
pii: embr.201846927
doi: 10.15252/embr.201846927
pmc: PMC6446200
pii:
doi:
Substances chimiques
Biomarkers
0
CX3C Chemokine Receptor 1
0
Cx3cr1 protein, mouse
0
Myd88 protein, mouse
0
Myeloid Differentiation Factor 88
0
Vascular Endothelial Growth Factor C
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2019 The Authors.
Références
Nat Rev Immunol. 2004 Jun;4(6):478-85
pubmed: 15173836
Inflamm Bowel Dis. 2013 Aug;19(9):1983-9
pubmed: 23835443
Nat Rev Immunol. 2011 Dec 09;12(1):9-23
pubmed: 22158411
Gastroenterology. 2016 Nov;151(5):923-932
pubmed: 27436071
J Exp Med. 2014 Jul 28;211(8):1571-83
pubmed: 25024136
Nat Rev Gastroenterol Hepatol. 2017 Sep;14(9):510-526
pubmed: 28655884
Blood. 2011 Jan 6;117(1):362-5
pubmed: 20962325
Science. 2016 Feb 19;351(6275):858-63
pubmed: 26822607
Am J Physiol Heart Circ Physiol. 2008 Nov;295(5):H2113-27
pubmed: 18849330
Nat Rev Gastroenterol Hepatol. 2015 Jan;12(1):14-25
pubmed: 25201040
Dev Dyn. 2007 Jul;236(7):2020-5
pubmed: 17576138
J Clin Invest. 2015 Nov 03;125(12):4572-86
pubmed: 26529256
Ann N Y Acad Sci. 2010 Oct;1207 Suppl 1:E21-8
pubmed: 20961303
Hepatology. 2015 May;61(5):1685-95
pubmed: 25643846
Immunity. 2014 Jul 17;41(1):21-35
pubmed: 25035951
EMBO Mol Med. 2015 Oct 12;7(11):1418-25
pubmed: 26459520
J Clin Invest. 2016 Jun 1;126(6):2167-80
pubmed: 27159393
Neurogastroenterol Motil. 2014 Jan;26(1):98-107
pubmed: 24329946
Nat Rev Microbiol. 2016 Jan;14(1):20-32
pubmed: 26499895
Circ Res. 2011 Aug 19;109(5):486-91
pubmed: 21778431
Proc Natl Acad Sci U S A. 2004 Nov 2;101(44):15718-23
pubmed: 15505215
World J Gastrointest Surg. 2012 Oct 27;4(10):228-33
pubmed: 23443404
JCI Insight. 2017 Aug 17;2(16):
pubmed: 28814666
J Clin Invest. 2015 Mar 2;125(3):926-38
pubmed: 25689247
Science. 2012 Jun 8;336(6086):1262-7
pubmed: 22674330
Vasc Cell. 2012 Sep 03;4(1):15
pubmed: 22943568
Nat Rev Mol Cell Biol. 2017 Aug;18(8):477-494
pubmed: 28537573
JCI Insight. 2017 Mar 23;2(6):e92465
pubmed: 28352669
Blood. 2013 Sep 26;122(13):2151-61
pubmed: 23836558
Nat Rev Neurosci. 2012 Oct;13(10):701-12
pubmed: 22968153
Nat Cell Biol. 2011 Sep 11;13(10):1202-13
pubmed: 21909098
Mucosal Immunol. 2015 Jan;8(1):152-60
pubmed: 24938744
Nat Immunol. 2010 May;11(5):373-84
pubmed: 20404851
J Clin Invest. 2015 Nov 2;125(11):4042-52
pubmed: 26436648
Science. 2014 Mar 28;343(6178):1249288
pubmed: 24625929
Immunity. 2017 Jun 20;46(6):910-926
pubmed: 28636959
Nature. 2012 Mar 11;483(7391):627-31
pubmed: 22407318
Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15451-5
pubmed: 12432102
J Cell Biol. 1962 Nov;15:259-77
pubmed: 14019085
Gut. 2010 Feb;59(2):197-206
pubmed: 19846409
Cell. 2014 Mar 27;157(1):121-41
pubmed: 24679531
Cell. 2015 Dec 3;163(6):1360-74
pubmed: 26638070
Trends Microbiol. 2014 May;22(5):261-6
pubmed: 24618403
J Clin Invest. 2011 Aug;121(8):2984-92
pubmed: 21765212
Cell Host Microbe. 2011 Oct 20;10(4):311-23
pubmed: 22018232
Cardiovasc Res. 2016 Sep;111(4):310-21
pubmed: 27357637
Annu Rev Immunol. 2010;28:623-67
pubmed: 20192812
Gut. 2008 Jan;57(1):1-4
pubmed: 18094195
Genes Dev. 2014 Jul 15;28(14):1592-603
pubmed: 25030698
Inflamm Bowel Dis. 2016 Jun;22(6):1326-45
pubmed: 26950310
J Immunol Methods. 2015 Jun;421:14-19
pubmed: 25599879
Science. 2012 Jun 8;336(6086):1268-73
pubmed: 22674334
FASEB J. 2007 Apr;21(4):1003-12
pubmed: 17210781
J Exp Med. 2018 Jan 2;215(1):35-49
pubmed: 29242199
Immunity. 2008 Aug 15;29(2):272-82
pubmed: 18656388
Nat Rev Immunol. 2013 May;13(5):321-35
pubmed: 23618829
Mol Cell Biol. 2008 Aug;28(15):4843-50
pubmed: 18519586
J Clin Invest. 2014 Sep;124(9):3863-78
pubmed: 25105363
Transgenic Res. 1999 Aug;8(4):265-77
pubmed: 10621974
Nat Protoc. 2016 Sep;11(9):1617-29
pubmed: 27560169
Am J Pathol. 2012 Mar;180(3):1273-82
pubmed: 22200616
Immunity. 1999 Oct;11(4):443-51
pubmed: 10549626
J Exp Med. 2016 Sep 19;213(10):1951-9
pubmed: 27551152
J Exp Med. 2007 Oct 1;204(10):2349-62
pubmed: 17846148
Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):13939-44
pubmed: 19666516
Circulation. 2012 Feb 21;125(7):872-82
pubmed: 22275501
JAMA Pediatr. 2013 Apr;167(4):374-9
pubmed: 23400224
Cell. 2015 Oct 8;163(2):354-66
pubmed: 26451485
Nat Immunol. 2016 Jan;17(1):18-25
pubmed: 26681458
Lab Invest. 1963 Mar;12:355-64
pubmed: 14010768
Inflamm Bowel Dis. 2013 Sep;19(10):2084-90
pubmed: 23851640
Infect Immun. 2010 Feb;78(2):639-50
pubmed: 19933833
J Clin Invest. 2014 Mar;124(3):936-42
pubmed: 24590279