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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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Bibliographische Detailangaben
Hauptverfasser: Tisch, Nathalie (VerfasserIn) , Mogler, Carolin (VerfasserIn) , Stojanovic, Ana (VerfasserIn) , Luck, Robert (VerfasserIn) , Korhonen, Emilia Anne (VerfasserIn) , Ellerkmann, Alexander (VerfasserIn) , Adler, Heike (VerfasserIn) , Singhal, Mahak (VerfasserIn) , Schermann, Géza (VerfasserIn) , Erkert, Lena (VerfasserIn) , Patankar, Jay V (VerfasserIn) , Karakatsani, Andromachi (VerfasserIn) , Scherr, Anna-Lena (VerfasserIn) , Fuchs, Yaron (VerfasserIn) , Cerwenka, Adelheid (VerfasserIn) , Wirtz, Stefan (VerfasserIn) , Köhler, Bruno Christian (VerfasserIn) , Augustin, Hellmut (VerfasserIn) , Becker, Christoph (VerfasserIn) , Schmidt, Thomas (VerfasserIn) , Ruiz de Almodóvar, Carmen (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 2 May 2022
In: EMBO molecular medicine
Year: 2022, Jahrgang: 14, Heft: 6, Pages: 1-21
ISSN:1757-4684
DOI:10.15252/emmm.202114121
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.15252/emmm.202114121
Verlag, kostenfrei, Volltext: https://www.embopress.org/doi/full/10.15252/emmm.202114121
Volltext
Verfasserangaben: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
Beschreibung
Zusammenfassung: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.
Beschreibung:Gesehen am 12.02.2024
Beschreibung:Online Resource
ISSN:1757-4684
DOI:10.15252/emmm.202114121

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