ArticleEMBO reports2019
A genome-wide screen identifies IRF2 as a key regulator of caspase-4 in human cells.
Article in EMBO reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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.
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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
56 citing papers in PubMed, 86 citations in OpenAlex.
- Role of the miR-340-5p/IRF1/USP18 Axis in Neuroinflammation Associated with Epilepsy.Neurochemical research · 2026Article
- Article
- An overview of human inflammasomes: Activation and regulation.Journal of immunology (Baltimore, Md. : 1950) · 2026Review
- IRF2 deficiency disrupts pyroptosis, NK cell interferon-γ production and resistance to Francisella.EMBO reports · 2026Article
- Rare epigenetic alterations are conserved across hematopoietic differentiation stages after mycobacterial infection.JCI insight · 2026Article
- Organelles and cancer cell pyroptosis: overview and perspectives.Cell death & disease · 2025Review
- New insights into the noncanonical inflammasome point to caspase-4 as a druggable target.Nature reviews. Immunology · 2025Review
- Functional Materials Targeted Regulation of Gasdermins: From Fundamentals to Functionalities and Applications.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- NLRP3 Inflammasome-Mediated Pyroptosis in Diabetic Nephropathy: Pathogenic Mechanisms and Therapeutic Targets.Journal of inflammation research · 2025Review
- Mechanisms and Targeted Therapeutic Strategies in Sepsis-Induced Myocardial Dysfunction: The Role of NLRP3 Inflammasome-Mediated Inflammation.Journal of inflammation research · 2025Review
- Pyroptosis-Related Gene Signatures Enable Robustly Diagnosis, Prognosis and Immune Responses Prediction in Uterine Corpus Endometrial Carcinoma.Journal of Cancer · 2025Article
- A CRISPR-Cas9 knockout screening identifies IRF2 as a key driver of OAS3/RNase L-mediated RNA decay during viral infection.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Transcriptional control of interferon-stimulated genes.The Journal of biological chemistry · 2024Review
- Gasdermins as evolutionarily conserved executors of inflammation and cell death.Nature cell biology · 2024Review
- Article
- The gasdermin family: emerging therapeutic targets in diseases.Signal transduction and targeted therapy · 2024Review
- Development of a Novel Pyroptosis-Associated lncRNA Biomarker Signature in Lung Adenocarcinoma.Molecular biotechnology · 2024Article
- The role and mechanism of pyroptosis and potential therapeutic targets in non-alcoholic fatty liver disease (NAFLD).Frontiers in cell and developmental biology · 2024Review
- Pyroptosis Inhibition in Disease Treatment: Opportunities and Challenges.Cell biochemistry and biophysics · 2023Review
- Role of gasdermin family proteins in cancers (Review).International journal of oncology · 2023Review
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15 authors at 2 institutions in 1 country.
Funding
Abstract
Caspase-4, the cytosolic LPS sensor, and gasdermin D, its downstream effector, constitute the non-canonical inflammasome, which drives inflammatory responses during Gram-negative bacterial infections. It remains unclear whether other proteins regulate cytosolic LPS sensing, particularly in human cells. Here, we conduct a genome-wide CRISPR/Cas9 screen in a human monocyte cell line to identify genes controlling cytosolic LPS-mediated pyroptosis. We find that the transcription factor, IRF2, is required for pyroptosis following cytosolic LPS delivery and functions by directly regulating caspase-4 levels in human monocytes and iPSC-derived monocytes. CASP4, GSDMD, and IRF2 are the only genes identified with high significance in this screen highlighting the simplicity of the non-canonical inflammasome. Upon IFN-γ priming, IRF1 induction compensates IRF2 deficiency, leading to robust caspase-4 expression. Deficiency in IRF2 results in dampened inflammasome responses upon infection with Gram-negative bacteria. This study emphasizes the central role of IRF family members as specific regulators of the non-canonical inflammasome.
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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.