ArticleThe Journal of biological chemistry2018
Inhibition of histone H3K27 demethylases selectively modulates inflammatory phenotypes of natural killer cells.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
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Who cites it
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.
- Targeting epigenetics and non-coding RNAs in atherosclerosis: from mechanisms to therapeutics.Pharmacology & therapeutics · 2019Pooled it
- Next-generation natural killer cell therapy: bench to bedside and beyond.Signal transduction and targeted therapy · 2026Review
- KDM6B inhibition modulates monocyte activation and alleviates IMQ-induced psoriasis-like skin inflammation.Cell communication and signaling : CCS · 2026Article
- Sepsis alters NK cell transcriptional programs for stress, actin remodeling, and intracellular trafficking.Cellular & molecular biology letters · 2026Article
- Bromodomain and extra-terminal protein inhibitors modulate natural killer cell function and differentiation.Scientific reports · 2026Article
- Unveiling the Role of Histone Methyltransferases in Psoriasis Pathogenesis: Insights from Transcriptomic Analysis.International journal of molecular sciences · 2025Article
- Chromatin-focused genetic and chemical screens identify BRPF1 as a targetable vulnerability in Taxol-resistant triple-negative breast cancer.Experimental & molecular medicine · 2025Article
- The epigenetic hallmarks of immune cells in cancer.Molecular cancer · 2025Review
- Histone demethylases in autophagy and inflammation.Cell communication and signaling : CCS · 2025Review
- The role of TERT C228T and KDM6A alterations and TME in NMIBC treated with BCG.NPJ precision oncology · 2024Article
- Combining single-cell and bulk RNA sequencing, NK cell marker genes reveal a prognostic and immune status in pancreatic ductal adenocarcinoma.Scientific reports · 2024Article
- No time to die: Epigenetic regulation of natural killer cell survival.Immunological reviews · 2024Review
- Comparative study ofScientific reports · 2024Article
- Epigenetic regulation in epithelial cells and innate lymphocyte responses toFrontiers in immunology · 2024Article
- Trained immunity in diabetes and hyperlipidemia: Emerging opportunities to target cardiovascular complications and design new therapies.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Review
- UTX deletion promotes M2 macrophage polarization by epigenetically regulating endothelial cell-macrophage crosstalk after spinal cord injury.Journal of nanobiotechnology · 2023Article
- Histone demethylases in the regulation of immunity and inflammation.Cell death discovery · 2023Review
- Epigenetic regulation and therapeutic targets in the tumor microenvironment.Molecular biomedicine · 2023Review
- Epigenetic regulation in the tumor microenvironment: molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2023Review
- Umifenovir Epigenetically Targets theMicrobiology spectrum · 2023Article
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 5 countries.
Funding
Abstract
Natural killer (NK) cells are innate lymphocytes, important in immune surveillance and elimination of stressed, transformed, or virus-infected cells. They critically shape the inflammatory cytokine environment to orchestrate interactions of cells of the innate and adaptive immune systems. Some studies have reported that NK cell activation and cytokine secretion are controlled epigenetically but have yielded only limited insight into the mechanisms. Using chemical screening with small-molecule inhibitors of chromatin methylation and acetylation, further validated by knockdown approaches, we here identified Jumonji-type histone H3K27 demethylases as key regulators of cytokine production in human NK cell subsets. The prototypic JMJD3/UTX (Jumonji domain-containing protein 3) H3K27 demethylase inhibitor GSK-J4 increased global levels of the repressive H3K27me3 mark around transcription start sites of effector cytokine genes. Moreover, GSK-J4 reduced IFN-γ, TNFα, granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin-10 levels in cytokine-stimulated NK cells while sparing their cytotoxic killing activity against cancer cells. The anti-inflammatory effect of GSK-J4 in NK cell subsets, isolated from peripheral blood or tissue from individuals with rheumatoid arthritis (RA), coupled with an inhibitory effect on formation of bone-resorbing osteoclasts, suggested that histone demethylase inhibition has broad utility for modulating immune and inflammatory responses. Overall, our results indicate that H3K27me3 is a dynamic and important epigenetic modification during NK cell activation and that JMJD3/UTX-driven H3K27 demethylation is critical for NK cell function.
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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.