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

Tisch N, Mogler C, Stojanovic A, Luck R, Korhonen EA, Ellerkmann A, Adler H, Singhal M, Schermann G, Erkert L, Patankar J, Karakatsani A, Scherr AL, Fuchs Y, Cerwenka A, Wirtz S, Koehler BC, Augustin HG, Becker C, Schmidt T, Ruiz De Almodovar C (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Embo Molecular Medicine Wiley-VCH Verlag / Wiley Open Access

DOI: 10.15252/emmm.202114121

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.

Authors with CRIS profile

Lena Erkert Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Jay Patankar Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Stefan Wirtz Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Christoph Becker Professur für Molekulare Gastroenterologie

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung

Related research project(s)

A076: Elucidating the regulation and function of Gasdermin C in intestinal infection and inflammation Feb. 1, 2020 - Jan. 31, 2023

Involved external institutions

Ruprecht-Karls-Universität Heidelberg DE Germany (DE) Universitätsklinikum Heidelberg DE Germany (DE) Technion - Israel Institute of Technology IL Israel (IL) Universität zu Köln DE Germany (DE) Technische Universität München (TUM) DE Germany (DE)

How to cite

APA:

Tisch, N., Mogler, C., Stojanovic, A., Luck, R., Korhonen, E.A., Ellerkmann, A.,... Ruiz De Almodovar, C. (2022). Caspase-8 in endothelial cells maintains gut homeostasis and prevents small bowel inflammation in mice. Embo Molecular Medicine. https://doi.org/10.15252/emmm.202114121

MLA:

Tisch, Nathalie, et al. "Caspase-8 in endothelial cells maintains gut homeostasis and prevents small bowel inflammation in mice." Embo Molecular Medicine (2022).

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