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

Détails

Ressource 1Télécharger: 34272244_BIB_3852082D8787.pdf (7936.15 [Ko])
Etat: Public
Version: Final published version
Licence: CC BY-NC 4.0
ID Serval
serval:BIB_3852082D8787
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
FOXC2 controls adult lymphatic endothelial specialization, function, and gut lymphatic barrier preventing multiorgan failure.
Périodique
Science advances
Auteur⸱e⸱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
Statut éditorial
Publié
Date de publication
07/2021
Peer-reviewed
Oui
Volume
7
Numéro
29
Pages
eabf4335
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Résumé
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.
Mots-clé
Endothelial Cells/metabolism, Endothelium, Lymphatic/metabolism, Endothelium, Lymphatic/pathology, Forkhead Transcription Factors/genetics, Forkhead Transcription Factors/metabolism, Humans, Lymphatic Vessels/metabolism, Lymphedema/metabolism, Lymphedema/pathology
Pubmed
Web of science
Open Access
Oui
Création de la notice
26/07/2021 10:01
Dernière modification de la notice
23/04/2022 6:35
Données d'usage