AI Article Synopsis
- The gut has a unique vascular barrier that regulates what gets into the bloodstream, but the details on how this barrier is maintained are not well understood.
- Researchers found that Caspase-8 is crucial for keeping the vascular barrier in the small intestine functioning properly, specifically in intestinal endothelial cells.
- When Caspase-8 is deleted from these cells, it causes bleeding and inflammation in the small intestine, showing that a healthy gut-vascular barrier is vital for preventing chronic gut issues.
Article 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.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9174885 | PMC |
| http://dx.doi.org/10.15252/emmm.202114121 | DOI Listing |
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