ArticleCell death and differentiation2023
Endothelial Caspase-8 prevents fatal necroptotic hemorrhage caused by commensal bacteria.
Article in Cell death and differentiation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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The trial behind it
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Who cites it
12 citing papers in PubMed, 15 citations in OpenAlex.
- Distinct types of regulated cell death in atherosclerosis.Journal of pharmaceutical analysis · 2026Review
- Changes in Expression Profiles of Caspase-8 and Mixed Lineage Kinase Domain-Like Protein/Receptor-Interacting Protein Kinase 3 Mediated by Inflammation in Cerebral Arteriovenous Malformations Associated With Clinical Condition on Admission.Journal of the American Heart Association · 2025Article
- Necroptotic cell death consequences and disease relevance.Nature immunology · 2025Review
- Alteration in Tracheal Morphology and Transcriptomic Features in Calves After Infection withMicroorganisms · 2025Article
- Transport functions of intestinal lymphatic vessels.Nature reviews. Gastroenterology & hepatology · 2025Review
- An immunohistochemical atlas of necroptotic pathway expression.EMBO molecular medicine · 2024Article
- ZBP1 and TRIF trigger lethal necroptosis in mice lacking caspase-8 and TNFR1.Cell death and differentiation · 2024Article
- The Function of Necroptosis and Its Treatment Target in IBD.Mediators of inflammation · 2024Review
- Mechanisms and functions of intestinal vascular specialization.The Journal of experimental medicine · 2024Review
- Phosphorylation-dependent pseudokinase domain dimerization drives full-length MLKL oligomerization.Nature communications · 2023Article
- New Dawn for Atherosclerosis: Vascular Endothelial Cell Senescence and Death.International journal of molecular sciences · 2023Review
- Death by TNF: a road to inflammation.Nature reviews. Immunology · 2023Review
Corrections and comments
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Authors and funding
21 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Caspase-8 transduces signals from death receptor ligands, such as tumor necrosis factor, to drive potent responses including inflammation, cell proliferation or cell death. This is a developmentally essential function because in utero deletion of endothelial Caspase-8 causes systemic circulatory collapse during embryogenesis. Whether endothelial Caspase-8 is also required for cardiovascular patency during adulthood was unknown. To address this question, we used an inducible Cre recombinase system to delete endothelial Casp8 in 6-week-old conditionally gene-targeted mice. Extensive whole body vascular gene targeting was confirmed, yet the dominant phenotype was fatal hemorrhagic lesions exclusively within the small intestine. The emergence of these intestinal lesions was not a maladaptive immune response to endothelial Caspase-8-deficiency, but instead relied upon aberrant Toll-like receptor sensing of microbial commensals and tumor necrosis factor receptor signaling. This lethal phenotype was prevented in compound mutant mice that lacked the necroptotic cell death effector, MLKL. Thus, distinct from its systemic role during embryogenesis, our data show that dysregulated microbial- and death receptor-signaling uniquely culminate in the adult mouse small intestine to unleash MLKL-dependent necroptotic hemorrhage after loss of endothelial Caspase-8. These data support a critical role for Caspase-8 in preserving gut vascular integrity in the face of microbial commensals.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.