ArticleImmunity2018
The Nuclear Receptor PPARγ Controls Progressive Macrophage Polarization as a Ligand-Insensitive Epigenomic Ratchet of Transcriptional Memory.
Article in Immunity, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 112 papers.
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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.
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.
Phase I Non-Randomized, Unblinded, Single-Center Trial of Oral Telmisartan Alone or Combined With Selected Standard of Care Therapies for Prostate Cancer
Phase II Non-Randomized, Unblinded, Single-Center Trial of Telmisartan in Combination With Cytotoxic Regimens in Platinum-Resistant Ovarian Cancer Versus Historical Best Supportive Care
Who cites it
112 citing papers in PubMed, 179 citations in OpenAlex.
- A transcriptional cofactor GRIP1 drives PPARγ DNA binding and p300-dependent enhancer activity during homeostatic macrophage polarization.Science advances · 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
- Synergistic interaction between the macrophage polarizing signals IL-4 and IFNγ is controlled by the STAT6/STAT1/IRF1 axis.Nucleic acids research · 2026Article
- CpG content contributes to tissue-resident macrophage enhancer selection.Nucleic acids research · 2026Article
- All-trans retinoic acid suppresses systemic inflammation induced by severe fever with thrombocytopenia syndrome virus in mice.Nature microbiology · 2026Article
- Siah2 is a lipid-mediated metabolic sensor in adipose tissue macrophage.Journal of lipid research · 2026Article
- Type 2 immune history imprints local training in nerve and airway associated interstitial macrophages (NAMs) for disease tolerance during lethal respiratory viral infection.Research square · 2026Article
- The gene regulatory networks shaping macrophage plasticity and altered function in fibrosis.Frontiers in immunology · 2026Review
- Long-Term Intestinal Epithelial Remodeling Induced by Acute Protein-Energy Malnutrition.bioRxiv : the preprint server for biology · 2025Article
- Impact of steroid differentiation on tumor microenvironment revealed by single-nucleus atlas of adrenal tumors.Nature communications · 2025Article
- Inhibition of salt-inducible kinases resolves autoimmune arthritis by promoting macrophage efferocytosis.Signal transduction and targeted therapy · 2025Article
- PPARγ acetylation governs mammary adenocarcinoma tumor growth via acetylated residues that determine DNA sequence-specific binding.Oncogene · 2025Article
- PPARG-centric transcriptional re-wiring during differentiation of human trophoblast stem cells into extravillous trophoblasts.Nucleic acids research · 2025Article
- Multifaceted regulatory mechanisms of the EGR family in tumours and prospects for therapeutic applications (Review).International journal of molecular medicine · 2025Review
- Galectin-12 in the Regulation of Sebocyte Proliferation, Lipid Metabolism, and Immune Responses.Biomolecules · 2025Review
- Myeloid but not hepatocytic CD38 is a key driver for hepatic ischemia/reperfusion injury.Signal transduction and targeted therapy · 2025Article
- Peroxisome proliferator-activated receptor alpha is an essential factor in enhanced macrophage immune function induced by angiotensin-converting enzyme.Cellular & molecular immunology · 2025Article
- Longitudinal single-cell profiles of lung regeneration after viral infection reveal persistent injury-associated cell states.Cell stem cell · 2025Article
52 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 6 institutions in 5 countries.
Funding
Abstract
Macrophages polarize into distinct phenotypes in response to complex environmental cues. We found that the nuclear receptor PPARγ drove robust phenotypic changes in macrophages upon repeated stimulation with interleukin (IL)-4. The functions of PPARγ on macrophage polarization in this setting were independent of ligand binding. Ligand-insensitive PPARγ bound DNA and recruited the coactivator P300 and the architectural protein RAD21. This established a permissive chromatin environment that conferred transcriptional memory by facilitating the binding of the transcriptional regulator STAT6 and RNA polymerase II, leading to robust production of enhancer and mRNAs upon IL-4 re-stimulation. Ligand-insensitive PPARγ binding controlled the expression of an extracellular matrix remodeling-related gene network in macrophages. Expression of these genes increased during muscle regeneration in a mouse model of injury, and this increase coincided with the detection of IL-4 and PPARγ in the affected tissue. Thus, a predominantly ligand-insensitive PPARγ:RXR cistrome regulates progressive and/or reinforcing macrophage polarization.
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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.