ArticleThe Journal of experimental medicine2010
PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps.
Article in The Journal of experimental medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 922 papers, 1 of them a synthesis that pooled it.
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Who cites it
922 citing papers in PubMed, 1 synthesis or guideline pooled it, 1,435 citations in OpenAlex.
- From immunological mechanisms to targeted therapies: a bibliometric analysis in the domain of research concerning neutrophil extracellular traps and pulmonary diseases (2006-2025).Frontiers in immunology · 2026Pooled it
- Association of NETs Markers with Clinical and Radiological Outcomes in Patients with Acute Ischemic Stroke Undergoing Thrombectomy: Does Heparin Treatment Modify This?Translational stroke research · 2025Trial
- Interfacial mild alkalinity shapes Neutrophil immunometabolism through sphingolipid remodeling to enhance antibacterial host defense.Materials today. Bio · 2026Article
- Breast Cancer-Derived AZU1 Educates Neutrophils to Promote Tumor Progression and Metastasis Through PAD4-Dependent Extracellular Trap Formation.Molecular carcinogenesis · 2026Article
- Review
- Neutrophil Extracellular Traps in the Tumor Microenvironment: Mechanisms, Immune Regulation, and Implications for Immune Checkpoint Inhibitor Therapy.International journal of molecular sciences · 2026Review
- Neutrophil extracellular traps in liver diseases: from molecular mechanisms to therapeutic interventions.Acta pharmacologica Sinica · 2026Review
- Review
- NETs mediate neuropathic pain in PSS-PN by participating in inflammatory injury to the vasa nervorum.Clinical rheumatology · 2026Article
- Antiviral innate immunity in myocarditis: mechanisms and emerging therapeutics.Experimental & molecular medicine · 2026Review
- NET-mediated immunothrombosis in ischemic stroke: pathobiology, biomarkers, and therapeutic targeting.Thrombosis journal · 2026Review
- Pulmonary Capillary Confinement Shapes A Motile Anuclear Neutrophil State.Research square · 2026Article
- Epigenetics in development, disease, and therapy: from mechanisms to clinical interventions.Science China. Life sciences · 2026Review
- Role of post-translational modifications in modulating histone reactivity in the extracellular environment.Biochemical Society transactions · 2026Review
- Chromatin decompaction within the nucleus increases plasma membrane tension promoting NETosis execution, independently of transcription.Nature communications · 2026Article
- Neutrophil extracellular traps promote liver metastasis by impairing NK cell-dependent tumor surveillance via CCDC25.Nature communications · 2026Article
- TLR7/9 and type I interferon signaling reprogram neutrophil NET responses and impair antibacterial defense in systemic lupus erythematosus.Cell press blue · 2026Article
- Neutrophil-Macrophage Interactions Shape Inflammatory Macrophage Remodeling in Gastric Cancer During Chemo-Immunotherapy.Cancer science · 2026Article
- Neutrophil extracellular traps in thrombosis of hematologic malignancies: Underlying mechanisms and therapeutic opportunities (Review).International journal of molecular medicine · 2026Review
- Multi-Omics Profiling Reveals Neutrophil Extracellular Trap Dysregulation in Diabetic Foot Ulcer Healing Impairment.International journal of molecular sciences · 2026Article
862 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Neutrophils trap and kill bacteria by forming highly decondensed chromatin structures, termed neutrophil extracellular traps (NETs). We previously reported that histone hypercitrullination catalyzed by peptidylarginine deiminase 4 (PAD4) correlates with chromatin decondensation during NET formation. However, the role of PAD4 in NET-mediated bacterial trapping and killing has not been tested. Here, we use PAD4 knockout mice to show that PAD4 is essential for NET-mediated antibacterial function. Unlike PAD4(+/+) neutrophils, PAD4(-/-) neutrophils cannot form NETs after stimulation with chemokines or incubation with bacteria, and are deficient in bacterial killing by NETs. In a mouse infectious disease model of necrotizing fasciitis, PAD4(-/-) mice are more susceptible to bacterial infection than PAD4(+/+) mice due to a lack of NET formation. Moreover, we found that citrullination decreased the bacterial killing activity of histones and nucleosomes, which suggests that PAD4 mainly plays a role in chromatin decondensation to form NETs instead of increasing histone-mediated bacterial killing. Our results define a role for histone hypercitrullination in innate immunity during bacterial infection.
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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.