ArticleJCI insight2020
Histone deacetylases 1 and 2 restrain CD4+ cytotoxic T lymphocyte differentiation.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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.
The trial behind it
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
19 citing papers in PubMed, 33 citations in OpenAlex.
- Epigenetic insights and innovations for overcoming barriers in CAR-T cell therapy for cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Cytotoxic CD4Signal transduction and targeted therapy · 2026Review
- Cytotoxic T lymphocytes and their dual role in modulating blood-brain barrier integrity in immune-mediated neurological pathologies.Journal of translational medicine · 2025Review
- Review
- Integrative network toxicology and molecular docking reveal 4-Nonylphenol's multifaceted mechanisms in breast cancer pathogenesis.PloS one · 2025Article
- CTLs heterogeneity and plasticity: implications for cancer immunotherapy.Molecular cancer · 2024Review
- Review
- Role of Histone Deacetylases in T-Cell Development and Function.International journal of molecular sciences · 2022Review
- Effects of Gut Microbiota on Host Adaptive Immunity Under Immune Homeostasis and Tumor Pathology State.Frontiers in immunology · 2022Review
- Human gut microbiota-reactive DP8α regulatory T cells, signature and related emerging functions.Frontiers in immunology · 2022Article
- Epigenetic strategies to boost CAR T cell therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Review
- Inhibition of HDAC1 alleviates monocrotaline-induced pulmonary arterial remodeling through up-regulation of miR-34a.Respiratory research · 2021Article
- Microbial short-chain fatty acids modulate CD8Nature communications · 2021Article
- Review
- Tumor-specific cytolytic CD4 T cells mediate immunity against human cancer.Science advances · 2021Article
- Targeting Histone Deacetylases to Modulate Graft-Versus-Host Disease and Graft-Versus-Leukemia.International journal of molecular sciences · 2020Review
- Article
- The Roles of Histone Deacetylases and Their Inhibitors in Cancer Therapy.Frontiers in cell and developmental biology · 2020Review
- Recent Update of HDAC Inhibitors in Lymphoma.Frontiers in cell and developmental biology · 2020Review
Corrections and comments
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Authors and funding
25 authors at 7 institutions in 3 countries.
Funding
Abstract
Some effector CD4+ T cell subsets display cytotoxic activity, thus breaking the functional dichotomy of CD4+ helper and CD8+ cytotoxic T lymphocytes. However, molecular mechanisms regulating CD4+ cytotoxic T lymphocyte (CD4+ CTL) differentiation are poorly understood. Here we show that levels of histone deacetylases 1 and 2 (HDAC1-HDAC2) are key determinants of CD4+ CTL differentiation. Deletions of both Hdac1 and 1 Hdac2 alleles (HDAC1cKO-HDAC2HET) in CD4+ T cells induced a T helper cytotoxic program that was controlled by IFN-γ-JAK1/2-STAT1 signaling. In vitro, activated HDAC1cKO-HDAC2HET CD4+ T cells acquired cytolytic activity and displayed enrichment of gene signatures characteristic of effector CD8+ T cells and human CD4+ CTLs. In vivo, murine cytomegalovirus-infected HDAC1cKO-HDAC2HET mice displayed a stronger induction of CD4+ CTL features compared with infected WT mice. Finally, murine and human CD4+ T cells treated with short-chain fatty acids, which are commensal-produced metabolites acting as HDAC inhibitors, upregulated CTL genes. Our data demonstrate that HDAC1-HDAC2 restrain CD4+ CTL differentiation. Thus, HDAC1-HDAC2 might be targets for the therapeutic induction of CD4+ CTLs.
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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.