ArticleProceedings of the National Academy of Sciences of the United States of America2012
Selective inhibition of CD4+ T-cell cytokine production and autoimmunity by BET protein and c-Myc inhibitors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.
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Who cites it
103 citing papers in PubMed, 184 citations in OpenAlex.
- Targeting miR-23a in CD8+ cytotoxic T lymphocytes prevents tumor-dependent immunosuppression.The Journal of clinical investigation · 2014Trial
- Bromodomain and extra-terminal protein inhibitors modulate natural killer cell function and differentiation.Scientific reports · 2026Article
- Brd4 expression in CD4 T cells and in microglia promotes neuroinflammation in experimental autoimmune encephalomyelitis.Journal of neuroinflammation · 2025Article
- Transcription factors in the development and treatment of immune disorders.Transcription · 2025Review
- Bromodomain and extra-terminal proteins in solid tumors: regulators of immune microenvironment and emerging therapeutic targets.Frontiers in immunology · 2025Review
- Development of a PET Probe Targeting Bromodomain and Extra-Terminal Proteins for In Vitro and In Vivo Visualization.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Targeting Interleukin-17 as a Novel Treatment Option for Fibrotic Diseases.Journal of clinical medicine · 2023Review
- Spinal-Specific Super Enhancer in Neuropathic Pain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- LC-MS/MS method for the quantitation of a dual PI3K/BRD4 inhibitor SF2523 in mouse plasma: Application to plasma protein binding and metabolism studies.Biomedical chromatography : BMC · 2023Article
- An αvβ3 integrin checkpoint is critical for efficient TNature immunology · 2023Article
- Type IV Collagen and SOX9 Are Molecular Targets of BET Inhibition in Experimental Glomerulosclerosis.International journal of molecular sciences · 2022Article
- Metabolic reprogramming and epigenetic modifications on the path to cancer.Protein & cell · 2022Review
- MYC-mediated silencing of miR-181a-5p promotes pathogenic Th17 responses by modulating AKT3-FOXO3 signaling.iScience · 2022Article
- How does age determine the development of human immune-mediated arthritis?Nature reviews. Rheumatology · 2022Review
- Inhibition of BET Family Proteins Suppresses African Swine Fever Virus Infection.Microbiology spectrum · 2022Article
- Blimp-1 molds the epigenetic architecture of IL-21-mediated autoimmune diseases through an autoregulatory circuit.JCI insight · 2022Article
- Epigenetic Modulation of Gremlin-1/NOTCH Pathway in Experimental Crescentic Immune-Mediated Glomerulonephritis.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Identification and validation of the role of c-Myc in head and neck squamous cell carcinoma.Frontiers in oncology · 2022Article
- Bromodomain Inhibitors Modulate FcγR-Mediated Mononuclear Phagocyte Activation and Chemotaxis.Frontiers in immunology · 2022Article
- A quinazoline-based bromodomain inhibitor, CN210, ameliorates indomethacin-induced ileitis in mice by inhibiting inflammatory cytokine expression.Drug development research · 2021Article
43 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
Bromodomain-containing proteins bind acetylated lysine residues on histone tails and are involved in the recruitment of additional factors that mediate histone modifications and enable transcription. A compound, I-BET-762, that inhibits binding of an acetylated histone peptide to proteins of the bromodomain and extra-terminal domain (BET) family, was previously shown to suppress the production of proinflammatory proteins by macrophages and block acute inflammation in mice. Here, we investigated the effect of short-term treatment with I-BET-762 on T-cell function. Treatment of naïve CD4(+) T cells with I-BET-762 during the first 2 d of differentiation had long-lasting effects on subsequent gene expression and cytokine production. Gene expression analysis revealed up-regulated expression of several antiinflammatory gene products, including IL-10, Lag3, and Egr2, and down-regulated expression of several proinflammatory cytokines including GM-CSF and IL-17. The short 2-d treatment with I-BET-762 inhibited the ability of antigen-specific T cells, differentiated under Th1 but not Th17 conditions in vitro, to induce pathogenesis in an adoptive transfer model of experimental autoimmune encephalomyelitis. The suppressive effects of I-BET-762 on T-cell mediated inflammation in vivo were accompanied by decreased recruitment of macrophages, consistent with decreased GM-CSF production by CNS-infiltrating T cells. These effects were mimicked by an inhibitor of c-myc function, implicating reduced expression of c-myc and GM-CSF as one avenue by which I-BET-762 suppresses the inflammatory functions of T cells. Our study demonstrates that inhibiting the functions of BET-family proteins during early T-cell differentiation causes long-lasting suppression of the proinflammatory functions of Th1 cells.
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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.