ArticleProceedings of the National Academy of Sciences of the United States of America2014
Type-I interferon signaling through ISGF3 complex is required for sustained Rip3 activation and necroptosis in macrophages.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
124 citing papers in PubMed, 192 citations in OpenAlex.
- The cGAS-STING/MITA pathway in innate antiviral immunity and beyond.Cell insight · 2026Review
- PANoptosis in the pathogenesis of myelodysplastic syndromes.Molecular oncology · 2026Review
- Lgr6Genes & diseases · 2026Review
- ISG15 negatively regulates RIPK3-mediated cell death and viral pathogenesis.Cell reports · 2026Article
- The critical role of necroptosis in oil cyst formation associated with autologous fat transplantation.Cell communication and signaling : CCS · 2026Article
- Metabolic Responses to Cyclic Fasting in Juvenile Turbot (Aquaculture nutrition · 2026Article
- Neuroinflammation and Disease: Pathways and Opportunities.Annual review of pharmacology and toxicology · 2026Review
- PANoptosis: A novel therapeutic target in kidney disease (Review).International journal of molecular medicine · 2025Review
- Molecular mechanisms of immune cell death in immunosenescence.Cell death and differentiation · 2025Review
- Dovitinib Ameliorates Inflammation-Related Diseases by Inhibiting Necroptosis and Ferroptosis.ACS chemical biology · 2025Article
- STING and Nonnecroptotic MLKL-Mediated Mechanisms Improve Dendritic Cell Maturation and Killing of Cancer Cells.European journal of immunology · 2025Article
- A viral necrosome mediates direct RIPK3 activation to promote inflammatory necroptosis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The Role of Post-Translational Modifications in Necroptosis.Biomolecules · 2025Review
- Mechanism of cell death and its application in the repair of inflammatory bowel disease by mesenchymal stem cells.Frontiers in immunology · 2025Review
- Necroptosis-based glioblastoma prognostic subtypes: implications for TME remodeling and therapy response.Annals of medicine · 2024Article
- Induced Necroptosis and Its Role in Cancer Immunotherapy.International journal of molecular sciences · 2024Review
- Identification of necroptosis genes and characterization of immune infiltration in non-alcoholic steatohepatitis.Hereditas · 2024Article
- Regulation of Zfp36 by ISGF3 and MK2 restricts the expression of inflammatory cytokines during necroptosis stimulation.Cell death & disease · 2024Article
- N-Myc and STAT Interactor is an Endometriosis Suppressor.International journal of molecular sciences · 2024Article
- Peroxiredoxin 6 suppresses ferroptosis in lung endothelial cells.Free radical biology & medicine · 2024Article
64 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 4 countries.
Funding
Abstract
Myeloid cells play a critical role in perpetuating inflammation during various chronic diseases. Recently the death of macrophages through programmed necrosis (necroptosis) has emerged as an important mechanism in inflammation and pathology. We evaluated the mechanisms that lead to the induction of necrotic cell death in macrophages. Our results indicate that type I IFN (IFN-I) signaling is a predominant mechanism of necroptosis, because macrophages deficient in IFN-α receptor type I (IFNAR1) are highly resistant to necroptosis after stimulation with LPS, polyinosinic-polycytidylic acid, TNF-α, or IFN-β in the presence of caspase inhibitors. IFN-I-induced necroptosis occurred through both mechanisms dependent on and independent of Toll/IL-1 receptor domain-containing adaptor inducing IFN-β (TRIF) and led to persistent phosphorylation of receptor-interacting protein 3 (Rip3) kinase, which resulted in potent necroptosis. Although various IFN-regulatory factors (IRFs) facilitated the induction of necroptosis in response to IFN-β, IRF-9-STAT1- or -STAT2-deficient macrophages were highly resistant to necroptosis. Our results indicate that IFN-β-induced necroptosis of macrophages proceeds through tonic IFN-stimulated gene factor 3 (ISGF3) signaling, which leads to persistent expression of STAT1, STAT2, and IRF9. Induction of IFNAR1/Rip3-dependent necroptosis also resulted in potent inflammatory pathology in vivo. These results reveal how IFN-I mediates acute inflammation through macrophage necroptosis.
Indexed as
Identifiers
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.