ArticleCell2018
Metabolic Induction of Trained Immunity through the Mevalonate Pathway.
Article in Cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 466 papers.
What it found
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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
466 citing papers in PubMed, 714 citations in OpenAlex.
- Biologic Mechanisms Underlying the Heterogeneous Response to Tight Glycemic Control among Differentially Inflamed Patients in the HALF-PINT Trial.American journal of respiratory and critical care medicine · 2025Trial
- Alendronate modulates cytokine responses in healthy young individuals after BCG vaccination.Immunology letters · 2024Trial
- Trained Immunity in Childhood Vaccination.Acta paediatrica (Oslo, Norway : 1992) · 2026Review
- The epigenetic-metabolic axis of trained immunity: dual roles in disease pathogenesis and intervention.Journal of molecular medicine (Berlin, Germany) · 2026Review
- Trained immunity in chronic, relapsing and low-grade joint inflammation.Nature reviews. Rheumatology · 2026Review
- Maturation-Dependent Constraints in the Ability of Human Monocytes to Initiate Trained Immunity.MedComm · 2026Article
- Convergent evolution of immune evasion in ESKAPE pathogens: A cross-pathogen architecture of conserved host-defense checkpoints.European journal of microbiology & immunology · 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
- Drugging trained immunity: immunometabolic and epigenetic control of maladaptive inflammatory memory in chronic inflammatory diseases.Immunologic research · 2026Review
- Review
- Review
- Hepatic stellate cell subpopulations in human MASLD-related hepatocellular carcinoma upregulate YAP via geranylgeranyl pyrophosphate.Hepatology communications · 2026Article
- Molecular Mechanisms and Therapeutic Targeting of the Macrophage Metabolic-Epigenetic Interaction Network in Chronic Obstructive Pulmonary Disease.Cell biochemistry and biophysics · 2026Review
- Maladaptive trained immunity as a hematopoietic stem cell driver of inflammaging.Nature aging · 2026Article
- Trained immunity: An unexplored component of IBD pathogenesis.Inflammatory bowel diseases · 2026Review
- Beyond Lipid Lowering: A Narrative Review and Expert Perspective on Precision Cardiovascular Prevention in People with HIV After REPRIEVE.Biomolecules · 2026Review
- Innate immunity: current understandings and future perspectives.Signal transduction and targeted therapy · 2026Review
- Article
- Spatial architecture of immunometabolism: Mitochondrial‑organelle interfaces in immune signaling (Review).International journal of molecular medicine · 2026Review
- Rediscovering eosinophil identity through tissue adaptation.Nature immunology · 2026Review
406 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Innate immune cells can develop long-term memory after stimulation by microbial products during infections or vaccinations. Here, we report that metabolic signals can induce trained immunity. Pharmacological and genetic experiments reveal that activation of the cholesterol synthesis pathway, but not the synthesis of cholesterol itself, is essential for training of myeloid cells. Rather, the metabolite mevalonate is the mediator of training via activation of IGF1-R and mTOR and subsequent histone modifications in inflammatory pathways. Statins, which block mevalonate generation, prevent trained immunity induction. Furthermore, monocytes of patients with hyper immunoglobulin D syndrome (HIDS), who are mevalonate kinase deficient and accumulate mevalonate, have a constitutive trained immunity phenotype at both immunological and epigenetic levels, which could explain the attacks of sterile inflammation that these patients experience. Unraveling the role of mevalonate in trained immunity contributes to our understanding of the pathophysiology of HIDS and identifies novel therapeutic targets for clinical conditions with excessive activation of trained immunity.
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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.