FOXC2 controls adult lymphatic endothelial specialization, function, and gut lymphatic barrier preventing multiorgan failure.

Details

Serval ID
serval:BIB_3852082D8787
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
FOXC2 controls adult lymphatic endothelial specialization, function, and gut lymphatic barrier preventing multiorgan failure.
Journal
Science advances
Author(s)
González-Loyola A., Bovay E., Kim J., Lozano T.W., Sabine A., Renevey F., Arroz-Madeira S., Rapin A., Wypych T.P., Rota G., Durot S., Velin D., Marsland B., Guarda G., Delorenzi M., Zamboni N., Luther S.A., Petrova T.V.
ISSN
2375-2548 (Electronic)
ISSN-L
2375-2548
Publication state
Published
Issued date
07/2021
Peer-reviewed
Oui
Volume
7
Number
29
Pages
eabf4335
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
The mechanisms maintaining adult lymphatic vascular specialization throughout life and their role in coordinating inter-organ communication to sustain homeostasis remain elusive. We report that inactivation of the mechanosensitive transcription factor Foxc2 in adult lymphatic endothelium leads to a stepwise intestine-to-lung systemic failure. Foxc2 loss compromised the gut epithelial barrier, promoted dysbiosis and bacterial translocation to peripheral lymph nodes, and increased circulating levels of purine metabolites and angiopoietin-2. Commensal microbiota depletion dampened systemic pro-inflammatory cytokine levels, corrected intestinal lymphatic dysfunction, and improved survival. Foxc2 loss skewed the specialization of lymphatic endothelial subsets, leading to populations with mixed, pro-fibrotic identities and to emergence of lymph node-like endothelial cells. Our study uncovers a cross-talk between lymphatic vascular function and commensal microbiota, provides single-cell atlas of lymphatic endothelial subtypes, and reveals organ-specific and systemic effects of dysfunctional lymphatics. These effects potentially contribute to the pathogenesis of diseases, such as inflammatory bowel disease, cancer, or lymphedema.
Pubmed
Web of science
Open Access
Yes
Create date
26/07/2021 9:01
Last modification date
04/09/2021 5:34
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