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

Autor: Tisch N; European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany., Mogler C; Institute of Pathology, TUM School of Medicine, Technical University of Munich, Munich, Germany., Stojanovic A; Department of Immunobiochemistry, Mannheim Institute for Innate Immunoscience (MI3), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany., Luck R; European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.; Division of Vascular Oncology and Metastasis, German Cancer Research Center Heidelberg (DKFZ-ZMBH Alliance), Heidelberg, Germany., Korhonen EA; European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany., Ellerkmann A; European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.; Department of General, Visceral and Transplantation Surgery, Heidelberg University, Heidelberg, Germany., Adler H; European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany., Singhal M; European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.; Division of Vascular Oncology and Metastasis, German Cancer Research Center Heidelberg (DKFZ-ZMBH Alliance), Heidelberg, Germany., Schermann G; European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany., Erkert L; Department of Medicine 1, Friedrich-Alexander-University, Erlangen, Germany., Patankar JV; Department of Medicine 1, Friedrich-Alexander-University, Erlangen, Germany., Karakatsani A; European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany., Scherr AL; National Center for Tumor Diseases, Department of Medical Oncology, Internal Medicine VI, Heidelberg University Hospital, Heidelberg, Germany., Fuchs Y; Laboratory of Stem Cell Biology & Regenerative Medicine, Department of Biology, Technion -Israel Institute of Technology, Haifa, Israel., Cerwenka A; European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.; Department of Immunobiochemistry, Mannheim Institute for Innate Immunoscience (MI3), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany., Wirtz S; Department of Medicine 1, Friedrich-Alexander-University, Erlangen, Germany., Köhler BC; National Center for Tumor Diseases, Department of Medical Oncology, Internal Medicine VI, Heidelberg University Hospital, Heidelberg, Germany., Augustin HG; European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.; Division of Vascular Oncology and Metastasis, German Cancer Research Center Heidelberg (DKFZ-ZMBH Alliance), Heidelberg, Germany., Becker C; Department of Medicine 1, Friedrich-Alexander-University, Erlangen, Germany., Schmidt T; Department of General, Visceral and Transplantation Surgery, Heidelberg University, Heidelberg, Germany.; Department of General, Visceral, Cancer and Transplantation Surgery, Faculty of Medicine with University Hospital Cologne, University of Cologne, Cologne, Germany., Ruiz de Almodóvar C; European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Jazyk: angličtina
Zdroj: EMBO molecular medicine [EMBO Mol Med] 2022 Jun 08; Vol. 14 (6), pp. e14121. Date of Electronic Publication: 2022 May 02.
DOI: 10.15252/emmm.202114121
Abstrakt: 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.
(© 2022 The Authors. Published under the terms of the CC BY 4.0 license.)
Databáze: MEDLINE
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