ArticlePloS one2015
PU.1 Suppresses Th2 Cytokine Expression via Silencing of GATA3 Transcription in Dendritic Cells.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 39 citations in OpenAlex.
- Trawling the depths of gene regulation: transcription-factor families orchestrating immunity in teleost fish.Frontiers in immunology · 2026Review
- Immune Mechanisms in Myocardial Remodeling Following Myocardial Infarction: Focusing on Regulatory Networks of T Cell Responses.Journal of inflammation research · 2026Review
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- Airway and parenchyma transcriptomics in a house dust mite model of experimental asthma.Respiratory research · 2023Article
- A Morbillivirus Infection Shifts DC Maturation Toward a Tolerogenic Phenotype to Suppress T Cell Activation.Journal of virology · 2022Article
- GATA3 Exerts Distinct Transcriptional Functions to Regulate Radiation Resistance in A549 and H1299 Cells.Oxidative medicine and cellular longevity · 2022Article
- NKL Homeobox Gene VENTX Is Part of a Regulatory Network in Human Conventional Dendritic Cells.International journal of molecular sciences · 2021Article
- PU.1 and IRF8 Modulate Activation of NLRP3 InflammasomeFrontiers in immunology · 2021Article
- PU.1 regulates Ccr7 gene expression by binding to its promoter in naïve CD4FEBS open bio · 2020Article
- Silencing of microRNA-494 inhibits the neurotoxic Th1 shift via regulating HDAC2-STAT4 cascade in ischaemic stroke.British journal of pharmacology · 2020Article
- Open Chromatin Profiling in Adipose Tissue Marks Genomic Regions with Functional Roles in Cardiometabolic Traits.G3 (Bethesda, Md.) · 2019Article
- Dendritic Cell-Mediated Th2 Immunity and Immune Disorders.International journal of molecular sciences · 2019Review
- A transcription factor PU.1 is critical for Ccl22 gene expression in dendritic cells and macrophages.Scientific reports · 2019Article
- Pleiotropic Effects of IL-33 on CD4Frontiers in immunology · 2019Review
- The effect of PU.1 knockdown on gene expression and function of mast cells.Scientific reports · 2018Article
- Effects of allergic stimulation and glucocorticoids on miR-155 in CD4American journal of clinical and experimental immunology · 2018Article
- Inflammatory responses induce an identity crisis of alveolar macrophages, leading to pulmonary alveolar proteinosis.The Journal of biological chemistry · 2017Article
- The Trophic Life Cycle Stage of the Opportunistic Fungal Pathogen Pneumocystis murina Hinders the Ability of Dendritic Cells To Stimulate CD4Infection and immunity · 2017Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The transcription factor PU.1 is predominantly expressed in dendritic cells (DCs) and is essential for DC differentiation. Although there are several reports that PU.1 positively regulates the expression of DC-specific genes, whether PU.1 also has a suppressive effect on DCs is largely unknown. Here we demonstrate that PU.1 suppresses the expression of Th2 cytokines including IL-13 and IL-5 in bone marrow-derived DCs (BMDCs), through repression of the expression of GATA3, which is a master regulator of Th2 differentiations. When PU.1 siRNA was introduced into BMDCs, LPS-induced expression of IL-13 and IL-5 was increased along with upregulation of the constitutive expression of GATA2 and GATA3. The additional introduction of GATA3 siRNA but not of GATA2 siRNA abrogated PU.1 siRNA-mediated upregulation of IL-13 and IL-5. A chromatin immunoprecipitation assay showed that PU.1 bound to Gata3 proximal promoter region, which is more dominant than the distal promoter in driving GATA3 transcription in DCs. The degree of histone acetylation at the Gata3 promoter was decreased in PU.1 siRNA-introduced DCs, suggesting the involvement of PU.1 in chromatin modification of the Gata3 promoter. Treatment with a histone deacetylase (HDAC) inhibitor, trichostatin A, increased the degree of histone H3 acetylation at the Gata3 promoter and induced the subsequent expression of GATA3. Experiments using HDAC inhibitors and siRNAs showed that HDAC3 suppressed GATA3 expression. The recruitment of HDAC3 to the Gata3 promoter was decreased by PU.1 knockdown. LPS-induced IL-13 expression was dramatically reduced in BMDCs generated from mice lacking the conserved GATA3 response element, termed CGRE, which is an essential site for the binding of GATA3 on the Il-13 promoter. The degree of H3K4me3 at CGRE was significantly increased in PU.1 siRNA-transfected stimulated DCs. Our results indicate that PU.1 plays pivotal roles in DC development and function, serving not only as a transcriptional activator but also as a repressor.
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