ArticleImmunity2020
FADD and Caspase-8 Regulate Gut Homeostasis and Inflammation by Controlling MLKL- and GSDMD-Mediated Death of Intestinal Epithelial Cells.
Article in Immunity, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 171 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
171 citing papers in PubMed, 2 syntheses or guidelines pooled it, 275 citations in OpenAlex.
- The therapeutic potential of mesenchymal stem cells in intestinal diseases: from mechanisms to clinical translation.Stem cell research & therapy · 2025Pooled it
- Review: the role of GSDMD in sepsis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022Pooled it
- Biological consequences of Z-nucleic acid sensing by ZBP1 and ADAR1.RNA biology · 2026Review
- The gasdermin family: from pyroptosis mechanisms to therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Mechanisms, regulation and clinical relevance of necroptosis.Nature reviews. Molecular cell biology · 2026Review
- cFLIP suppresses caspase-1- and MLKL-independent perinatal lethality driven by auto-processing impaired caspase-8 D387A.Cell death and differentiation · 2026Article
- Human ZBP1 is a potent inducer of cell death through mechanisms divergent from mouse ZBP1.EMBO reports · 2026Article
- The kinase domain of RIPK3 tunes its scaffolding functions.Cell death and differentiation · 2026Article
- Caspase-8 silences cell death-independent constitutive immune activation driven by tonic TNF-α.EMBO reports · 2026Article
- Oncogenic KRAS-driven type I interferon signalling primes pancreatic cancer for necroptosis.Nature communications · 2026Article
- Targeting programmed cell death: a novel therapeutic paradigm for cancer based on mode-of-death classification.Apoptosis : an international journal on programmed cell death · 2026Review
- Z-nucleic acid-mediated PANoptosis in infection, inflammation, and cancer.Communications biology · 2026Review
- The role and mechanism of TNFRSF21 in promoting necroptosis of vascular endothelial cells and inducing vascular leakage in sepsis.Journal of molecular medicine (Berlin, Germany) · 2026Article
- Herpes simplex virus 1 harboring poly(T) DNA sequences as a key ligand for AIM2 inflammasome activation and host defense.Nature communications · 2026Article
- RIPK3 sequentially recruits MLKL and RIPK1 to induce PANoptosis and chemokine production.Cell death and differentiation · 2026Article
- The landscape of regulated cell death: It's all downhill from here.Molecular cell · 2026Review
- DDIT3 drives nucleus pulposus cell PANoptosis and intervertebral disc degeneration progression.Apoptosis : an international journal on programmed cell death · 2026Article
- PANoptosis: a new perspective for targeting programmed cell death after spinal cord injury.Frontiers in immunology · 2026Review
- Monogenic disorders of the TNF signalling pathway.Nature reviews. Rheumatology · 2026Review
- Emapunil attenuates ulcerative colitis by suppressing Z-DNA binding protein 1 driven pyroptosis and pro-inflammatory polarization in macrophages.Frontiers in immunology · 2026Article
111 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Pathways controlling intestinal epithelial cell (IEC) death regulate gut immune homeostasis and contribute to the pathogenesis of inflammatory bowel diseases. Here, we show that caspase-8 and its adapter FADD act in IECs to regulate intestinal inflammation downstream of Z-DNA binding protein 1 (ZBP1)- and tumor necrosis factor receptor-1 (TNFR1)-mediated receptor interacting protein kinase 1 (RIPK1) and RIPK3 signaling. Mice with IEC-specific FADD or caspase-8 deficiency developed colitis dependent on mixed lineage kinase-like (MLKL)-mediated epithelial cell necroptosis. However, MLKL deficiency fully prevented ileitis caused by epithelial caspase-8 ablation, but only partially ameliorated ileitis in mice lacking FADD in IECs. Our genetic studies revealed that caspase-8 and gasdermin-D (GSDMD) were both required for the development of MLKL-independent ileitis in mice with epithelial FADD deficiency. Therefore, FADD prevents intestinal inflammation downstream of ZBP1 and TNFR1 by inhibiting both MLKL-induced necroptosis and caspase-8-GSDMD-dependent pyroptosis-like death of epithelial cells.
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What OpenQuestion holds
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.