Caspase-8 in endothelial cells maintains gut homeostasis and prevents small bowel inflammation in mice.
EMBO Mol Med
; 14(6): e14121, 2022 06 08.
Article
in En
| MEDLINE
| ID: mdl-35491615
ABSTRACT
The gut has a specific vascular barrier that controls trafficking of antigens and microbiota into the bloodstream. However, the molecular mechanisms regulating the maintenance of this vascular barrier remain elusive. Here, we identified Caspase-8 as a pro-survival factor in mature intestinal endothelial cells that is required to actively maintain vascular homeostasis in the small intestine in an organ-specific manner. In particular, we find that deletion of Caspase-8 in endothelial cells results in small intestinal hemorrhages and bowel inflammation, while all other organs remained unaffected. We also show that Caspase-8 seems to be particularly needed in lymphatic endothelial cells to maintain gut homeostasis. Our work demonstrates that endothelial cell dysfunction, leading to the breakdown of the gut-vascular barrier, is an active driver of chronic small intestinal inflammation, highlighting the role of the intestinal vasculature as a safeguard of organ function.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Endothelial Cells
/
Caspase 8
/
Intestinal Mucosa
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
EMBO Mol Med
Journal subject:
BIOLOGIA MOLECULAR
Year:
2022
Document type:
Article
Affiliation country: