ArticleScientific reports2022
Screening of compounds to identify novel epigenetic regulatory factors that affect innate immune memory in macrophages.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 27 citations in OpenAlex.
- Dissection of MAPK and NF-κB p65 signaling dynamics underlying LPS tolerance in macrophages at the single-cell level.Biotechnology reports (Amsterdam, Netherlands) · 2026Article
- The M1/M2 Test System for Determining Macrophage Phenotypes.International journal of molecular sciences · 2026Review
- Microglial epigenetic memory is associated with accelerated resolution of inflammatory pain induced by prophylactic macrophage-derived small extracellular vesicles.bioRxiv : the preprint server for biology · 2026Article
- Microglial Epigenetic Memory is Associated with Accelerated Resolution of Inflammatory Pain Induced by Prophylactic Macrophage-Derived Small Extracellular Vesicles.Journal of inflammation research · 2026Article
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- Glucan-Based Nanoparticles Empower Precision Cancer Immunotherapy: Design Strategies, Immune Reprogramming Mechanisms, and Clinical Translation Prospects.International journal of nanomedicine · 2026Review
- Age-Dependent Regulation of Hippocampal Inflammation by the Mitochondrial Translocator Protein in Mice.Aging cell · 2025Article
- Effect of mRNA formulated with lipid nanoparticles on the transcriptomic and epigenetic profiles of F4/80Scientific reports · 2025Article
- A polycomb group protein EED epigenetically regulates responses in lipopolysaccharide tolerized macrophages.Epigenetics & chromatin · 2024Article
- Loss of OScientific reports · 2024Article
- Identification of memory mechanism in tissue-resident stem cells via ANGPTL4 beyond immune cells upon viral antigen exposure.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Exploring Memory Function Beyond Immune Cells: ANGPTL4-Mediated Memory Functions in Tissue Resident Stem Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Epigenetic regulation of innate immune dynamics during inflammation.Journal of leukocyte biology · 2024Review
- OiScience · 2024Article
- Less Severe Polymicrobial Sepsis in ConditionalInternational journal of molecular sciences · 2023Article
- Less Severe Lipopolysaccharide-Induced Inflammation in ConditionalInternational journal of molecular sciences · 2023Article
- Less Severe Sepsis in Cecal Ligation and Puncture Models with and without Lipopolysaccharide in Mice with ConditionalInternational journal of molecular sciences · 2023Article
- The Regulatory Roles ofInternational journal of molecular sciences · 2023Article
- Trained immunity as a potential target for therapeutic immunomodulation in Duchenne muscular dystrophy.Frontiers in immunology · 2023Review
- Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Trained immunity and tolerance are part of the innate immune memory that allow innate immune cells to differentially respond to a second encounter with stimuli by enhancing or suppressing responses. In trained immunity, treatment of macrophages with β-glucan (BG) facilitates the production of proinflammatory cytokines upon lipopolysaccharide (LPS) stimulation. For the tolerance response, LPS stimulation leads to suppressed inflammatory responses during subsequent LPS exposure. Epigenetic reprogramming plays crucial roles in both phenomena, which are tightly associated with metabolic flux. In this study, we performed a screening of an epigenetics compound library that affects trained immunity or LPS tolerance in macrophages using TNFα as a readout. Among the 181 compounds tested, one compound showed suppressive effects, while 2 compounds showed promoting effects on BG-trained TNFα production. In contrast, various inhibitors targeting Aurora kinase, histone methyltransferase, histone demethylase, histone deacetylase and DNA methyltransferase showed inhibitory activity against LPS tolerance. Several proteins previously unknown to be involved in innate immune memory, such as MGMT, Aurora kinase, LSD1 and PRMT5, were revealed. Protein network analysis revealed that the trained immunity targets are linked via Trp53, while LPS tolerance targets form three clusters of histone-modifying enzymes, cell division and base-excision repair. In trained immunity, the histone lysine methyltransferase SETD7 was identified, and its expression was increased during BG treatment. Level of the histone lysine demethylase, LSD1, increased during LPS priming and siRNA-mediated reduction resulted in increased expression of Il1b in LPS tolerance. Taken together, this screening approach confirmed the importance of epigenetic modifications in innate immune memory and provided potential novel targets for intervention.
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