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Caspase-8 in endothelial cells maintains gut homeostasis and prevents small bowel inflammation in mice

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 endothe...

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Main Authors: Tisch, Nathalie (Author) , Mogler, Carolin (Author) , Stojanovic, Ana (Author) , Luck, Robert (Author) , Korhonen, Emilia Anne (Author) , Ellerkmann, Alexander (Author) , Adler, Heike (Author) , Singhal, Mahak (Author) , Schermann, Géza (Author) , Erkert, Lena (Author) , Patankar, Jay V (Author) , Karakatsani, Andromachi (Author) , Scherr, Anna-Lena (Author) , Fuchs, Yaron (Author) , Cerwenka, Adelheid (Author) , Wirtz, Stefan (Author) , Köhler, Bruno Christian (Author) , Augustin, Hellmut (Author) , Becker, Christoph (Author) , Schmidt, Thomas (Author) , Ruiz de Almodóvar, Carmen (Author)
Format: Article (Journal)
Language:English
Published: 2 May 2022
In: EMBO molecular medicine
Year: 2022, Volume: 14, Issue: 6, Pages: 1-21
ISSN:1757-4684
DOI:10.15252/emmm.202114121
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.15252/emmm.202114121
Verlag, kostenfrei, Volltext: https://www.embopress.org/doi/full/10.15252/emmm.202114121
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Author Notes:Nathalie Tisch, Carolin Mogler, Ana Stojanovic, Robert Luck, Emilia A Korhonen, Alexander Ellerkmann, Heike Adler, Mahak Singhal, Géza Scherman, Lena Erkert, Jay V Patankar, Andromachi Karakatsani, Anna-Lena Scherr, Yaron Fuchs, Adelheid Cerwenka, Stefan Wirtz, Bruno Christian Köhler, Hellmut G Augustin, Christoph Becker, Thomas Schmidt and Carmen Ruiz de Almodóvar
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Summary: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.
Item Description:Gesehen am 12.02.2024
Physical Description:Online Resource
ISSN:1757-4684
DOI:10.15252/emmm.202114121

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