ArticleNature immunology2017
Type I interferons and the cytokine TNF cooperatively reprogram the macrophage epigenome to promote inflammatory activation.
Article in Nature immunology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 158 papers, 1 of them a synthesis that pooled it.
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Who cites it
158 citing papers in PubMed, 1 synthesis or guideline pooled it, 237 citations in OpenAlex.
- Meta-Analysis ofFrontiers in immunology · 2019Pooled it
- Insights from integrative spatial transcriptomics in sepsis-associated acute kidney injury.Nature reviews. Nephrology · 2026Review
- Long-term immunoprophylaxis by TLR9 ligand mediates macrophage-ILC cross-talk against respiratory viral infection.Science advances · 2026Article
- Clonal lineage tracing of innate immune cells in human cancer.Cancer cell · 2026Article
- Striking the right balance with type I interferon signalling in cancer.Nature reviews. Cancer · 2026Review
- Defined culture conditions improve functional properties of mature iPSC-derived macrophages for therapeutic screening.Stem cell research & therapy · 2026Article
- Epigenetic dysregulation of IRF9 drives excessive interferon signaling in COPD.EMBO molecular medicine · 2026Article
- Epromoters bind key stress-related transcription factors to regulate clusters of stress response genes.The EMBO journal · 2026Article
- Immune activation of primary human macrophages is suppressed by the coordinated action ofmBio · 2026Article
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- HDAC3-driven immunometabolic reprogramming in type 2 diabetes and its complications: from enzymatic deacetylation to non-enzymatic scaffolding.Frontiers in immunology · 2026Review
- Immune and Immune-Integrated Organoids as NextGeneration Platforms for Disease Modeling.MedComm · 2025Review
- Gut bacteriophages induce specific-reprogramming of macrophages to generate a protective innate immunity response to lipopolysaccharide exposure.Gut microbes · 2025Article
- The sex-biased chromatin modifier SMC1A promotes autoimmunity by shaping inflammatory pathways in patients with SLE.Nature communications · 2025Article
- The Type I Interferon Axis in Systemic Autoimmune Diseases: From Molecular Pathways to Targeted Therapy.Biomolecules · 2025Review
- STING Agonist-Loaded Physalis Mottle Virus-like Particles as a Potent Prophylactic for Metastatic Melanoma.ACS applied materials & interfaces · 2025Article
- Beyond Antagonism: IL-4 Exploits TNF signaling to Shape Its Gene Expression Signature in Monocytes and Macrophages.bioRxiv : the preprint server for biology · 2025Article
- Type 1 interferon signature and allograft inflammatory factor-1 contribute to refractoriness to TNF inhibition in ankylosing spondylitis.Nature communications · 2025Article
- Semaphorin4B is elevated in rheumatoid arthritis and enhances the inflammatory phenotype of macrophages and fibroblast-like synoviocytes.Arthritis research & therapy · 2025Article
98 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 2 countries.
Funding
Abstract
Cross-regulation of Toll-like receptor (TLR) responses by cytokines is essential for effective host defense, avoidance of toxicity and homeostasis, but the underlying mechanisms are not well understood. Our comprehensive epigenomics approach to the analysis of human macrophages showed that the proinflammatory cytokines TNF and type I interferons induced transcriptional cascades that altered chromatin states to broadly reprogram responses induced by TLR4. TNF tolerized genes encoding inflammatory molecules to prevent toxicity while preserving the induction of genes encoding antiviral and metabolic molecules. Type I interferons potentiated the inflammatory function of TNF by priming chromatin to prevent the silencing of target genes of the transcription factor NF-κB that encode inflammatory molecules. The priming of chromatin enabled robust transcriptional responses to weak upstream signals. Similar chromatin regulation occurred in human diseases. Our findings reveal that signaling crosstalk between interferons and TNF is integrated at the level of chromatin to reprogram inflammatory responses, and identify previously unknown functions and mechanisms of action of these cytokines.
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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.