ArticleThe Journal of clinical investigation2017
TNF superfamily receptor OX40 triggers invariant NKT cell pyroptosis and liver injury.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 63 citations in OpenAlex.
- TRAF6, a gga-miR-7b Target, PromotesBiomolecules · 2026Article
- OX40 signaling in cancer immunotherapy: mechanisms of action, translational applications, and therapeutic perspectives.Frontiers in immunology · 2026Review
- Bendamustine switches TNF receptor superfamily signal from a survival to a death signal in B-cell lymphomas.Blood neoplasia · 2025Article
- Antioxidant interventions reduced cytokine-induced pyroptosis of peripheral MAIT cells in patients with HBV-related cirrhosis.Hepatology communications · 2025Article
- Unveiling the nexus: pyroptosis and its crucial implications in liver diseases.Molecular and cellular biochemistry · 2025Review
- GSDMD-mediated pyroptosis: molecular mechanisms, diseases and therapeutic targets.Molecular biomedicine · 2025Review
- Invariant Natural Killer T lymphocytes as natural sensors for microbes: a two-edged sword in liver diseases.Frontiers in immunology · 2025Review
- Molecular Mechanism of TRAF6 in Malignant Proliferation of Human NK/T Cell Lymphoma Cell HANK1.Mediterranean journal of hematology and infectious diseases · 2025Article
- Gpx4 Regulates Invariant NKT Cell Homeostasis and Function by Preventing Lipid Peroxidation and Ferroptosis.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- CCR2+TREM-1+ monocytes promote natural killer T cell dysfunction contributing towards HBV disease progression.Immunologic research · 2024Article
- [Research progress on pyroptosis in liver diseases].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2024Article
- Hypermethylation of the glutathione peroxidase 4 promoter predicts poor prognosis in patients with hepatitis B virus-associated acute-on-chronic liver failure.Frontiers in molecular biosciences · 2024Article
- Different types of cell death and their shift in shaping disease.Cell death discovery · 2023Review
- Classic costimulatory interactions in MAIT cell responses: from gene expression to immune regulation.Clinical and experimental immunology · 2023Article
- Programmed Cell Death in Liver Fibrosis.Journal of inflammation research · 2023Review
- Hepatic HRC induces hepatocyte pyroptosis and HSCs activation via NLRP3/caspase-1 pathway.Journal of molecular medicine (Berlin, Germany) · 2022Article
- The emerging role of pyroptosis in pediatric cancers: from mechanism to therapy.Journal of hematology & oncology · 2022Review
- Insights into inflammasome regulation: cellular, molecular, and pathogenic control of inflammasome activation.Immunologic research · 2022Review
- Multi-faceted role of pyroptosis mediated by inflammasome in liver fibrosis.Journal of cellular and molecular medicine · 2022Review
- Aberrant blood MALT1 and its relevance with multiple organic dysfunctions, T helper cells, inflammation, and mortality risk of sepsis patients.Journal of clinical laboratory analysis · 2022Article
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12 authors at 3 institutions in 2 countries.
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Abstract
Tissue-resident immune cells play a key role in local and systemic immune responses. The liver, in particular, hosts a large number of invariant natural killer T (iNKT) cells, which are involved in diverse immune responses. However, the mechanisms that regulate survival and homeostasis of liver iNKT cells are poorly defined. Here we have found that liver iNKT cells constitutively express the costimulatory TNF superfamily receptor OX40 and that OX40 stimulation results in massive pyroptotic death of iNKT cells, characterized by the release of potent proinflammatory cytokines that induce liver injury. This OX40/NKT pyroptosis pathway also plays a key role in concanavalin A-induced murine hepatitis. Mechanistically, we demonstrated that liver iNKT cells express high levels of caspase 1 and that OX40 stimulation activates caspase 1 via TNF receptor-associated factor 6-mediated recruitment of the paracaspase MALT1. We also found that activation of caspase 1 in iNKT cells results in processing of pro-IL-1β to mature IL-1β as well as cleavage of the pyroptotic protein gasdermin D, which generates a membrane pore-forming fragment to produce pyroptotic cell death. Thus, our study has identified OX40 as a death receptor for iNKT cells and uncovered a molecular mechanism of pyroptotic cell death. These findings may have important clinical implications in the development of OX40-directed therapies.
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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.