Tisch, Nathalie ORCID: 0000-0003-0019-4346, Mogler, Carolin, Stojanovic, Ana, Luck, Robert, Korhonen, Emilia A., Ellerkmann, Alexander, Adler, Heike, Singhal, Mahak ORCID: 0000-0002-7303-9585, Schermann, Geza, Erkert, Lena, Patankar, Jay, V, Karakatsani, Andromachi, Scherr, Anna-Lena, Fuchs, Yaron, Cerwenka, Adelheid, Wirtz, Stefan, Koehler, Bruno Christian, Augustin, Hellmut G., Becker, Christoph ORCID: 0000-0002-1388-1041, Schmidt, Thomas and Ruiz de Almodovar, Carmen (2022). Caspase-8 in endothelial cells maintains gut homeostasis and prevents small bowel inflammation in mice. EMBO Mol. Med., 14 (6). HOBOKEN: WILEY. ISSN 1757-4684

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Tisch, NathalieUNSPECIFIEDorcid.org/0000-0003-0019-4346UNSPECIFIED
Mogler, CarolinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stojanovic, AnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Luck, RobertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Korhonen, Emilia A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ellerkmann, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Adler, HeikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Singhal, MahakUNSPECIFIEDorcid.org/0000-0002-7303-9585UNSPECIFIED
Schermann, GezaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Erkert, LenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Patankar, Jay, VUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Karakatsani, AndromachiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scherr, Anna-LenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fuchs, YaronUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cerwenka, AdelheidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wirtz, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koehler, Bruno ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Augustin, Hellmut G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Becker, ChristophUNSPECIFIEDorcid.org/0000-0002-1388-1041UNSPECIFIED
Schmidt, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ruiz de Almodovar, CarmenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-689739
DOI: 10.15252/emmm.202114121
Journal or Publication Title: EMBO Mol. Med.
Volume: 14
Number: 6
Date: 2022
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 1757-4684
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MIXED LINEAGE KINASE; LYMPHATIC VASCULATURE; EPITHELIAL BARRIER; DOMAIN-LIKE; B-CELLS; DEATH; NECROPTOSIS; DOWNSTREAM; NECROSIS; IMMUNITYMultiple languages
Medicine, Research & ExperimentalMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/68973

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