ArticleThe Journal of experimental medicine2021
Bromodomain protein BRD4 directs and sustains CD8 T cell differentiation during infection.
Article in The Journal of experimental medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 36 citations in OpenAlex.
- Targeting the cytokine-epigenetic axis: a new paradigm and prospects for disease treatment.European cytokine network · 2026Review
- Optimal transport fate mapping resolves T cell differentiation dynamics across tissues.bioRxiv : the preprint server for biology · 2026Article
- Epigenetic regulation of T cell exhaustion in cancer.Nature reviews. Cancer · 2026Review
- pH sensing and inflammation: linking acidic microenvironments to immune reprogramming.Frontiers in immunology · 2026Review
- Regulation of T cell exhaustion and stemness: molecular mechanisms and implications for cancer immunotherapy.Cellular & molecular immunology · 2026Review
- BRD4 inhibition leads to MDSC apoptosis and enhances checkpoint blockade therapy.The Journal of clinical investigation · 2025Article
- BACH2 promotes seeding and establishment of long-lived HIV-1 reservoir in memory CD4Cell reports. Medicine · 2025Article
- Article
- BRD4 as the key lactylation related gene in heart failure identified through bioinformatics analysis.Scientific reports · 2025Article
- Targeting BRD4 to attenuate RANKL-induced osteoclast activation and bone erosion in rheumatoid arthritis.Molecular and cellular biochemistry · 2025Article
- Bromodomain and extra-terminal proteins in solid tumors: regulators of immune microenvironment and emerging therapeutic targets.Frontiers in immunology · 2025Review
- Brd4 modulates metabolic endotoxemia-induced inflammation by regulating colonic macrophage infiltration in high-fat diet-fed mice.Communications biology · 2024Article
- BET inhibition reforms the immune microenvironment and alleviates T cell dysfunction in chronic lymphocytic leukemia.JCI insight · 2024Article
- Cellular and molecular waypoints along the path of T cell exhaustion.Science immunology · 2023Review
- Epigenetic Regulation of Leukocyte Inflammatory Mediator Production Dictates Staphylococcus aureus Craniotomy Infection Outcome.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Effects of epigenetic therapy on natural killer cell function and development in hematologic malignancy.Journal of leukocyte biology · 2023Review
- BET inhibitors rescue anti-PD1 resistance by enhancing TCF7 accessibility in leukemia-derived terminally exhausted CD8Leukemia · 2023Article
- Intimate communications within the tumor microenvironment: stromal factors function as an orchestra.Journal of biomedical science · 2023Review
- Regulation of programmed cell death by Brd4.Cell death & disease · 2022Review
- Epigenetic engineering for optimal chimeric antigen receptor T cell therapy.Cancer science · 2022Review
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Authors and funding
23 authors at 7 institutions in 1 country.
Funding
Abstract
In response to infection, pathogen-specific CD8 T cells differentiate into functionally diverse effector and memory T cell populations critical for resolving disease and providing durable immunity. Through small-molecule inhibition, RNAi studies, and induced genetic deletion, we reveal an essential role for the chromatin modifier and BET family member BRD4 in supporting the differentiation and maintenance of terminally fated effector CD8 T cells during infection. BRD4 bound diverse regulatory regions critical to effector T cell differentiation and controlled transcriptional activity of terminal effector-specific super-enhancers in vivo. Consequentially, induced deletion of Brd4 or small molecule-mediated BET inhibition impaired maintenance of a terminal effector T cell phenotype. BRD4 was also required for terminal differentiation of CD8 T cells in the tumor microenvironment in murine models, which we show has implications for immunotherapies. Taken together, these data reveal an unappreciated requirement for BRD4 in coordinating activity of cis regulatory elements to control CD8 T cell fate and lineage stability.
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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 Socratic graph.