ArticleImmunity2022
The epigenetic state of IL-4-polarized macrophages enables inflammatory cistromic expansion and extended synergistic response to TLR ligands.
Article in Immunity, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.
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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
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Immunological Activity of Vaccine Systems Containing Liposomal Nanocarriers against Protozoan-induced Diseases: A Systematic Review.Current medicinal chemistry · 2025Pooled it
- Transcriptional regulation and function of GPR18 in macrophage subtype specification.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Multi-level transcriptional control of specific macrophage responses.The EMBO journal · 2026Review
- Pan-cancer epigenetic landscape of human tumor-associated macrophages reveals crucial enhancers governing their heterogenous formation by Pol II pausing modulation.Journal of advanced research · 2026Article
- Regulation of immune signal integration and memory by inflammation-induced chromosome conformation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Coenzyme A activates TLR4 and enhances alternative macrophage activation in line with MyD88 agonism.EMBO reports · 2026Article
- Synergistic interaction between the macrophage polarizing signals IL-4 and IFNγ is controlled by the STAT6/STAT1/IRF1 axis.Nucleic acids research · 2026Article
- Responses of Nasal Polyp-Derived Macrophages to Inflammatory Cues and Potential Pathological Roles in Type 2 Chronic Rhinosinusitis With Nasal Polyps.Clinical and experimental otorhinolaryngology · 2026Article
- Lactiplantibacillus plantarum SLpl116 attenuates OVA-induced food allergy with ecological restoration of the gut microbiota and immune rebalancing.NPJ science of food · 2026Article
- SHIP blocks (MDP + LPS)-induced synergy in macrophages independent of catalytic activity.Journal of leukocyte biology · 2026Article
- BACH1 orchestrates macrophage state transitions to coordinate regenerative inflammation.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Characterization of p16-positive stromal cells in age-related cardiac disorders.Journal of biochemistry · 2026Article
- Immunotherapies based on macrophage reprogramming in periodontitis and apical periodontitis.Clinical oral investigations · 2026Review
- A Photothermal Transducer Regulates Transmembrane Calcium Flow for Synergistic Osteoarthritis Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- CD14+CD16- monocytes exhibit NF-κB hyperactivation in biliary atresia: Clinical association and murine therapeutic validation.Hepatology communications · 2026Article
- Beyond M1/M2: The Pivotal Role of Macrophage Metabolic Reprogramming in Chronic Bone Disease and Targeted Intervention.International journal of molecular sciences · 2026Review
- Article
- Phytochemical Monomers Derived from Traditional Chinese Medicine May Prevent and Treat Atherosclerosis by Modulating the Macrophage Mitochondrial-Lysosomal Senescence Axis.International journal of general medicine · 2026Review
- Toll-like receptors in innate immunity and inflammation: from fundamental biology to clinic insights.Immunity & inflammation · 2026Review
- Regulation of macrophage polarization in chronic airway inflammatory diseases: immune interactions, metabolic reprogramming, and beyond.Frontiers in immunology · 2026Review
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Authors and funding
20 authors at 3 institutions in 2 countries.
Funding
Abstract
Prior exposure to microenvironmental signals could fundamentally change the response of macrophages to subsequent stimuli. It is believed that T helper-2 (Th2)-cell-type cytokine interleukin-4 (IL-4) and Toll-like receptor (TLR) ligand-activated transcriptional programs mutually antagonize each other, and no remarkable convergence has been identified between them. In contrast, here, we show that IL-4-polarized macrophages established a hyperinflammatory gene expression program upon lipopolysaccharide (LPS) exposure. This phenomenon, which we termed extended synergy, was supported by IL-4-directed epigenomic remodeling, LPS-activated NF-κB-p65 cistrome expansion, and increased enhancer activity. The EGR2 transcription factor contributed to the extended synergy in a macrophage-subtype-specific manner. Consequently, the previously alternatively polarized macrophages produced increased amounts of immune-modulatory factors both in vitro and in vivo in a murine Th2 cell-type airway inflammation model upon LPS exposure. Our findings establish that IL-4-induced epigenetic reprogramming is responsible for the development of inflammatory hyperresponsiveness to TLR activation and contributes to lung pathologies.
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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.