ArticleThe Journal of biological chemistry2014
Histone deacetylase inhibitors modulate interleukin 6-dependent CD4+ T cell polarization in vitro and in vivo.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.
- Histone and Histone Acetylation-Related Alterations of Gene Expression in Uninvolved Psoriatic Skin and Their Effects on Cell Proliferation, Differentiation, and Immune Responses.International journal of molecular sciences · 2023Pooled it
- Epigenetic Alterations in Microbiome-Host Interactions in Inflammatory and Autoimmune Diseases.International journal of molecular sciences · 2026Review
- Liposomal Delivery ofPharmaceutics · 2026Article
- HDAC7 controls anti-viral and anti-tumor immunity by CD8Frontiers in immunology · 2026Article
- Selenium: A Key Element in Inflammatory Bowel Disease.Antioxidants (Basel, Switzerland) · 2025Review
- Epigenetic Regulation in Ischemic Neuroprotection: The Dual Role of HDACs and HATs in Neuroinflammation and Recovery.Antioxidants (Basel, Switzerland) · 2025Review
- Alleviation of Acute Heat Stress in Broiler Chickens by Dietary Supplementation of Polyphenols from Shredded, Steam-Exploded Pine Particles.Microorganisms · 2025Article
- Bioinformatic analysis identifies LPL as a critical gene in diabetic kidney disease via lipoprotein metabolism.Frontiers in endocrinology · 2025Article
- Histone deacetylase in inflammatory bowel disease: novel insights.Therapeutic advances in gastroenterology · 2025Review
- Repurposing Histone Deacetylase Inhibitors for Management of Solid Organ Transplant Rejection.Results and problems in cell differentiation · 2025Review
- Mesenchymal stem cells-derived extracellular vesicles ameliorate lupus nephritis by regulating T and B cell responses.Stem cell research & therapy · 2024Article
- Class IIa HDAC4 and HDAC7 cooperatively regulate gene transcription in Th17 cell differentiation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Propionate functions as a feeding state-dependent regulatory metabolite to counter proinflammatory signaling linked to nutrient load and obesity.Journal of leukocyte biology · 2024Article
- Histone deacetylase 1 and 3 inhibitors alleviate colon inflammation by inhibiting Th17 cell differentiation.Journal of clinical laboratory analysis · 2022Article
- Nuciferine Regulates Immune Function and Gut Microbiota in DSS-Induced Ulcerative Colitis.Frontiers in veterinary science · 2022Article
- T Helper Cell Lineage-Defining Transcription Factors: Potent Targets for Specific GVHD Therapy?Frontiers in immunology · 2021Review
- Intestinal Inflammation is Linked to Hypoacetylation of Histone 3 Lysine 27 and can be Reversed by Valproic Acid Treatment in Inflammatory Bowel Disease Patients.Cellular and molecular gastroenterology and hepatology · 2021Observational
- Histone Deacetylase Isoforms Differentially Modulate Inflammatory and Autoantibody Responses in a Mouse Model of Myasthenia Gravis.Frontiers in neurology · 2021Article
- Targeting epigenetics as atherosclerosis treatment: an updated view.Current opinion in lipidology · 2020Review
- Targeting Histone Deacetylases to Modulate Graft-Versus-Host Disease and Graft-Versus-Leukemia.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Histone deacetylase (HDAC) inhibitors have been associated primarily with an anti-proliferative effect in vitro and in vivo. Recent data provide evidence for an anti-inflammatory potency of HDAC inhibitors in models of experimental colitis. Because the balance of T cell subpopulations is critical for the balance of the mucosal immune system, this study explores the regulatory potency of HDAC inhibitors on T cell polarization as a mechanistic explanation for the observed anti-inflammatory effects. Although HDAC inhibition suppressed the polarization toward the pro-inflammatory T helper 17 (Th17) cells, it enhanced forkhead box P3 (FoxP3)(+) regulatory T cell polarization in vitro and in vivo at the site of inflammation in the lamina propria. This was paralleled by a down-regulation of the interleukin 6 receptor (IL-6R) on naïve CD4(+) T cells on the mRNA as well as on the protein level and changes in the chromatin acetylation at the IL6R gene and its promoter. Downstream of the IL-6R, HDAC inhibition was followed by a decrease in STAT3 phosphorylation as well as retinoic acid receptor-related orphan receptor γT (RORγT) expression, thus identifying the IL-6/STAT3/IL-17 pathway as an important target of HDAC inhibitors. These results directly translated to experimental colitis, where IL-6R expression was suppressed in naïve T cells, paralleled by a significant reduction of Th17 cells in the lamina propria of ITF2357-treated animals, resulting in the amelioration of disease. This study indicates that, in experimental colitis, inhibition of HDAC exerts an anti-inflammatory potency by directing T helper cell polarization via targeting the IL-6 pathway.
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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.