ArticleImmunity2018
The Transcription Factor STAT6 Mediates Direct Repression of Inflammatory Enhancers and Limits Activation of Alternatively Polarized Macrophages.
Article in Immunity, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 161 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
161 citing papers in PubMed, 1 synthesis or guideline pooled it, 240 citations in OpenAlex.
- Epigenetic Underpinnings of Inflammation: A Key to Unlock the Tumor Microenvironment in Glioblastoma.Frontiers in immunology · 2022Pooled it
- Understanding the Variability of Peanut-Oral Immunotherapy Responses by Multi-Omics Profiling of Immune Cells.Allergy · 2025Trial
- Transcriptional regulation and function of GPR18 in macrophage subtype specification.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Engineering IL-4 resistant proinflammatory human myeloid cells for cancer immunotherapy.Molecular oncology · 2026Article
- Multi-level transcriptional control of specific macrophage responses.The EMBO journal · 2026Review
- 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
- Integrated multi-omics identifies lineage-dependent myeloid cells recruitment and the APP-CD74 axis as an immunoregulatory target in pediatric high-grade glioma.Acta neuropathologica · 2026Article
- CpG content contributes to tissue-resident macrophage enhancer selection.Nucleic acids research · 2026Article
- Synergistic interaction between the macrophage polarizing signals IL-4 and IFNγ is controlled by the STAT6/STAT1/IRF1 axis.Nucleic acids research · 2026Article
- Exercise-Induced Skeletal Muscle Secretory Factors and Macrophage Functional Remodeling: Mechanistic Advances.International journal of molecular sciences · 2026Review
- Tumor necrosis factor-α-stimulated gene 6 promotes hematoma clearance after intracerebral hemorrhage in a mouse model.Neural regeneration research · 2026Article
- Macrophage-derived oxysterols organize T helper 2 cells to suppress type 1 inflammation during pulmonary fungal infection.Science immunology · 2026Article
- Activating an interleukin 4-FLT3-STAT6 axis in multipotent progenitors restores lymphopoiesis in inflammation and aging.Immunity · 2026Article
- Epoxy Clerodane Diterpene Attenuates the Differentiated Adipocyte Hypertrophy and Enhances Mitochondrial Metabolism.ChemistryOpen · 2026Article
- STAT Signaling in Metabolic Disorders: From Molecular Mechanisms to Therapeutic Implications.Cell biochemistry and biophysics · 2026Review
- Roles of efferocytosis in wound repair: Process, cells, and signals.Genes & diseases · 2026Review
- IL-4/STAT6-signaling Influences Local Inflammation and Regeneration Processes During Acute Pancreatitis and Promotes Fibrosis by a Direct Activation of Pancreatic Fibroblasts During Chronic Pancreatitis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- DNA-PK-mediated phosphorylation of STAT6 establishes a non-canonical type 2 immunity axis to prevent macrophage senescence.Nature communications · 2026Article
- Mechanisms of tumor-derived extracellular vesicle-mediated immunometabolic reprogramming and immunotherapeutic resistance.Molecular cancer · 2026Review
- The gene regulatory networks shaping macrophage plasticity and altered function in fibrosis.Frontiers in immunology · 2026Review
101 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
21 authors at 8 institutions in 5 countries.
Funding
Abstract
The molecular basis of signal-dependent transcriptional activation has been extensively studied in macrophage polarization, but our understanding remains limited regarding the molecular determinants of repression. Here we show that IL-4-activated STAT6 transcription factor is required for the direct transcriptional repression of a large number of genes during in vitro and in vivo alternative macrophage polarization. Repression results in decreased lineage-determining transcription factor, p300, and RNA polymerase II binding followed by reduced enhancer RNA expression, H3K27 acetylation, and chromatin accessibility. The repressor function of STAT6 is HDAC3 dependent on a subset of IL-4-repressed genes. In addition, STAT6-repressed enhancers show extensive overlap with the NF-κB p65 cistrome and exhibit decreased responsiveness to lipopolysaccharide after IL-4 stimulus on a subset of genes. As a consequence, macrophages exhibit diminished inflammasome activation, decreased IL-1β production, and pyroptosis. Thus, the IL-4-STAT6 signaling pathway establishes an alternative polarization-specific epigenenomic signature resulting in dampened macrophage responsiveness to inflammatory stimuli.
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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.