ArticleThe EMBO journal2023
Caspase-8-driven apoptotic and pyroptotic crosstalk causes cell death and IL-1β release in X-linked inhibitor of apoptosis (XIAP) deficiency.
Article in The EMBO journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 59 citations in OpenAlex.
- The NLRP3 inflammasome at the crossroads of innate immune signaling and cell death.Cellular & molecular immunology · 2026Review
- Gasdermin-Mediated Pyroptosis: Novel Strategies Against Colorectal Cancer.Cancer science · 2026Review
- Targeting E3 ubiquitin ligases: Mechanistic breakthroughs and novel clinical translation pathways for tumor radioimmunotherapy.Molecular cancer · 2026Review
- XIAP Deficiency Impairs Colonic Tuft Cell Development and Predisposes to Crohn's Disease.MedComm · 2026Article
- Integrative Analysis Identifies PANoptosis-Associated Molecular Patterns and Immune Alterations in Rat Cerebral Ischemic-Reperfusion Injury.Cellular and molecular neurobiology · 2026Article
- Caspase-1 in cancer and inflammatory diseases: a potential therapeutic target.Apoptosis : an international journal on programmed cell death · 2026Review
- TNF superfamily member 14 drives post-influenza depletion of alveolar macrophages, enabling secondary pneumococcal pneumonia.The Journal of clinical investigation · 2026Article
- Fuzheng Jiedu formula attenuates acute pneumonia by coordinated regulation of macrophage NLRP3 inflammasome and neutrophil NETs.Chinese medicine · 2026Article
- Macrophage pyroptosis in inflammatory bowel disease: mechanistic insights, pathological roles and treatment strategies.Frontiers in immunology · 2026Review
- Resident phagocytes promote non-cell-autonomous fragmentation of apoptotic cells.Science advances · 2025Article
- TREM1 facilitates nonresponse to anti-TNF-α monoclonal antibodies in colitis via boosting ITCH/TAK1/caspase-8 axis-mediated macrophage pyroptosis.Journal of translational medicine · 2025Article
- The Salmonella pathogenicity island 1 injectisome reprograms host cell translation to evade the inflammatory response.Nature communications · 2025Article
- Review
- NLRP3 inflammasome-driven hemophagocytic lymphohistiocytosis occurs independent of IL-1β and IL-18 and is targetable by BET inhibitors.Science advances · 2025Article
- Mechanistic insights into gasdermin-mediated pyroptosis.Nature reviews. Molecular cell biology · 2025Review
- Role of Peripheral NLRP3 Inflammasome in Cognitive Impairments: Insights of Non-central Factors.Molecular neurobiology · 2025Review
- New insights into pulmonary arterial hypertension: interaction between PANoptosis and perivascular inflammatory responses.Apoptosis : an international journal on programmed cell death · 2025Review
- PANoptosis: a potential target of atherosclerotic cardiovascular disease.Apoptosis : an international journal on programmed cell death · 2025Review
- Targeting regulated cell death: Apoptosis, necroptosis, pyroptosis, ferroptosis, and cuproptosis in anticancer immunity.Journal of translational internal medicine · 2025Article
- Exploring Ubiquitination in Spinal Cord Injury Therapy: Multifaceted Targets and Promising Strategies.Neurochemical research · 2025Review
Corrections and comments
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Authors and funding
30 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genetic lesions in X-linked inhibitor of apoptosis (XIAP) pre-dispose humans to cell death-associated inflammatory diseases, although the underlying mechanisms remain unclear. Here, we report that two patients with XIAP deficiency-associated inflammatory bowel disease display increased inflammatory IL-1β maturation as well as cell death-associated caspase-8 and Gasdermin D (GSDMD) processing in diseased tissue, which is reduced upon patient treatment. Loss of XIAP leads to caspase-8-driven cell death and bioactive IL-1β release that is only abrogated by combined deletion of the apoptotic and pyroptotic cell death machinery. Namely, extrinsic apoptotic caspase-8 promotes pyroptotic GSDMD processing that kills macrophages lacking both inflammasome and apoptosis signalling components (caspase-1, -3, -7, -11 and BID), while caspase-8 can still cause cell death in the absence of both GSDMD and GSDME when caspase-3 and caspase-7 are present. Neither caspase-3 and caspase-7-mediated activation of the pannexin-1 channel, or GSDMD loss, prevented NLRP3 inflammasome assembly and consequent caspase-1 and IL-1β maturation downstream of XIAP inhibition and caspase-8 activation, even though the pannexin-1 channel was required for NLRP3 triggering upon mitochondrial apoptosis. These findings uncouple the mechanisms of cell death and NLRP3 activation resulting from extrinsic and intrinsic apoptosis signalling, reveal how XIAP loss can co-opt dual cell death programs, and uncover strategies for targeting the cell death and inflammatory pathways that result from XIAP deficiency.
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