ArticleJCI insight2020
Cholesterol 25-hydroxylase promotes efferocytosis and resolution of lung inflammation.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 72 citations in OpenAlex.
- Aggressive breast cancers secrete heme metabolites to alter macrophage immune suppression and function.Communications biology · 2026Article
- [Mechanisms of Macrophage Efferocytosis-driven Remodeling of Lung Cancer Microenvironment Structure and Angiogenesis and Prospects for Clinical Intervention].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Review
- MARCH2 prevents doxorubicin-induced cardiomyopathy by stabilizing NR1H2 and promoting clearance of apoptotic cardiomyocytes.Nature communications · 2026Article
- Single-cell transcriptomics reveal alveolar macrophage-specific responses in single-hit ozone exposure model in mice.American journal of physiology. Lung cellular and molecular physiology · 2026Article
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- The sterols-LXR axis alleviates IL-17-mediated acute inflammatory response inMarine life science & technology · 2026Article
- Metabolic-epigenetic imprinting of macrophages in endometriosis: a working model for lesion persistence and treatment.Frontiers in immunology · 2026Review
- Heterogeneity of Lung Phagocytes and Clearance of Apoptotic Cells in Lung Injury and Repair.Seminars in respiratory and critical care medicine · 2025Review
- Review
- Adiponectin pathway activation dampens inflammation and enhances alveolar macrophage fungal killing via LC3-associated phagocytosis.PLoS pathogens · 2025Article
- Roles of 4'-International journal of molecular sciences · 2024Article
- Cholesterol sensing and metabolic adaptation in tissue immunity.Trends in immunology · 2024Review
- Cholesterol and Cholesterol-Lowering Medications in COVID-19-An Unresolved Matter.International journal of molecular sciences · 2024Review
- MerTK Induces Dysfunctional Dendritic Cells by Metabolic Reprogramming.Cancer immunology research · 2024Article
- Adiponectin pathway activation dampens inflammation and enhances alveolar macrophage fungal killing via LC3-associated phagocytosis.bioRxiv : the preprint server for biology · 2024Article
- Tissue-Resident Alveolar Macrophages Reduce Ozone-induced Inflammation via MerTK-mediated Efferocytosis.American journal of respiratory cell and molecular biology · 2024Article
- Enhancing CAR Macrophage Efferocytosis Via Surface Engineered Lipid Nanoparticles Targeting LXR Signaling.Advanced materials (Deerfield Beach, Fla.) · 2024Article
- The role of cholesterol and its oxidation products in tuberculosis pathogenesis.Immunometabolism (Cobham, Surrey) · 2024Review
- Novel insights into brain lipid metabolism in Alzheimer's disease: Oligodendrocytes and white matter abnormalities.FEBS open bio · 2024Review
- 25-Hydroxycholesterol in health and diseases.Journal of lipid research · 2024Review
Corrections and comments
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Authors and funding
19 authors at 8 institutions in 1 country.
Funding
Abstract
Alveolar macrophages (AM) play a central role in initiation and resolution of lung inflammation, but the integration of these opposing core functions is poorly understood. AM expression of cholesterol 25-hydroxylase (CH25H), the primary biosynthetic enzyme for 25-hydroxycholesterol (25HC), far exceeds the expression of macrophages in other tissues, but no role for CH25H has been defined in lung biology. As 25HC is an agonist for the antiinflammatory nuclear receptor, liver X receptor (LXR), we speculated that CH25H might regulate inflammatory homeostasis in the lung. Here, we show that, of natural oxysterols or sterols, 25HC is induced in the inflamed lung of mice and humans. Ch25h-/- mice fail to induce 25HC and LXR target genes in the lung after LPS inhalation and exhibit delayed resolution of airway neutrophilia, which can be rescued by systemic treatment with either 25HC or synthetic LXR agonists. LXR-null mice also display delayed resolution, suggesting that native oxysterols promote resolution. During resolution, Ch25h is induced in macrophages upon their encounter with apoptotic cells and is required for LXR-dependent prevention of AM lipid overload, induction of Mertk, efferocytic resolution of airway neutrophilia, and induction of TGF-β. CH25H/25HC/LXR is, thus, an inducible metabolic axis that programs AMs for efferocytic resolution of inflammation.
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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.