ArticleJournal of immunology (Baltimore, Md. : 1950)2015
Inhibiting STAT5 by the BET bromodomain inhibitor JQ1 disrupts human dendritic cell maturation.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 60 citations in OpenAlex.
- 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
- Strategies to therapeutically modulate cytokine action.Nature reviews. Drug discovery · 2023Review
- The Epigenetic Reader Protein SP140 Regulates Dendritic Cell Activation, Maturation and Tolerogenic Potential.Current issues in molecular biology · 2023Article
- Article
- Recent research on the association between signal transducer and activator of transcription 5 and childhood acute lymphoblastic leukemia.Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2022Review
- Bromodomain Inhibitors Modulate FcγR-Mediated Mononuclear Phagocyte Activation and Chemotaxis.Frontiers in immunology · 2022Article
- BET Protein Inhibition Regulates Macrophage Chromatin Accessibility and Microbiota-Dependent Colitis.Frontiers in immunology · 2022Article
- Role of miR-2392 in driving SARS-CoV-2 infection.Cell reports · 2021Article
- The BET family in immunity and disease.Signal transduction and targeted therapy · 2021Review
- Inhibition of Bromodomain and Extra Terminal (BET) Domain Activity Modulates the IL-23R/IL-17 Axis and Suppresses Acute Graft-Frontiers in oncology · 2021Article
- Selective BET-bromodomain inhibition by JQ1 suppresses dendritic cell maturation and antigen-specific T-cell responses.Cancer immunology, immunotherapy : CII · 2021Article
- Dendritic Cells: Versatile Players in Renal Transplantation.Frontiers in immunology · 2021Review
- Epigenetic Mechanisms of Resistance to Immune Checkpoint Inhibitors.Biomolecules · 2020Review
- Tolerogenic Dendritic Cells: The Pearl of Immunotherapy in Organ Transplantation.Frontiers in immunology · 2020Review
- STAT5: a Target of Antagonism by Neurotropic Flaviviruses.Journal of virology · 2019Article
- Balancing STAT Activity as a Therapeutic Strategy.Cancers · 2019Review
- The next-generation BET inhibitor, PLX51107, delays melanoma growth in a CD8-mediated manner.Pigment cell & melanoma research · 2019Article
- Molecular regulation of dendritic cell development and function in homeostasis, inflammation, and cancer.Molecular immunology · 2019Review
- Fine-Tuning Cytokine Signals.Annual review of immunology · 2019Review
Corrections and comments
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Authors and funding
8 authors at 6 institutions in 4 countries.
Funding
Abstract
Maturation of dendritic cells (DCs) is required to induce T cell immunity, whereas immature DCs can induce immune tolerance. Although the transcription factor STAT5 is suggested to participate in DC maturation, its role in this process remains unclear. In this study, we investigated the effect of STAT5 inhibition on LPS-induced maturation of human monocyte-derived DCs (Mo-DCs). We inhibited STAT5 by treating Mo-DCs with JQ1, a selective inhibitor of BET epigenetic readers, which can suppress STAT5 function. We found that JQ1 inhibits LPS-induced STAT5 phosphorylation and nuclear accumulation, thereby attenuating its transcriptional activity in Mo-DCs. The diminished STAT5 activity results in impaired maturation of Mo-DCs, as indicated by defective upregulation of costimulatory molecules and CD83, as well as reduced secretion of IL-12p70. Expression of constitutively activated STAT5 in JQ1-treated Mo-DCs overcomes the effects of JQ1 and enhances the expression of CD86, CD83, and IL-12. The activation of STAT5 in Mo-DCs is mediated by GM-CSF produced following LPS stimulation. Activated STAT5 then leads to increased expression of both GM-CSF and GM-CSFR, triggering an autocrine loop that further enhances STAT5 signaling and enabling Mo-DCs to acquire a more mature phenotype. JQ1 decreases the ability of Mo-DCs to induce allogeneic CD4(+) and CD8(+) T cell proliferation and production of proinflammatory cytokines. Furthermore, JQ1 leads to a reduced generation of inflammatory CD8(+) T cells and decreased Th1 differentiation. Thus, JQ1 impairs LPS-induced Mo-DC maturation by inhibiting STAT5 activity, thereby generating cells that can only weakly stimulate an adaptive-immune response. Therefore, JQ1 could have beneficial effects in treating T cell-mediated inflammatory diseases.
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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.