ArticleJournal of immunology (Baltimore, Md. : 1950)2014
Ezh2 regulates transcriptional and posttranslational expression of T-bet and promotes Th1 cell responses mediating aplastic anemia in mice.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 64 citations in OpenAlex.
- EZH2 and intracellular CaCellular & molecular immunology · 2026Article
- Exploring the role of EZH2 in neuroinflammation: implications for innovative therapeutic strategies.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Mechanisms and Therapeutic Implications of EZH2 in Nasal Diseases.Clinical reviews in allergy & immunology · 2025Review
- Increased age-associated B cells in patients with acquired aplastic anemia correlate with IFN-γ.Blood advances · 2024Article
- Unraveling trajectories from aplastic anemia to hematologic malignancies: genetic and molecular insights.Frontiers in oncology · 2024Article
- Targeting KDM2A Enhances T-cell Infiltration in NSD1-Deficient Head and Neck Squamous Cell Carcinoma.Cancer research · 2023Article
- The pleiotropic roles of EZH2 in T-cell immunity and immunotherapy.International journal of hematology · 2022Review
- Levamisole Suppresses CD4Frontiers in immunology · 2022Article
- Metabolic reprogramming by miRNAs in the tumor microenvironment: Focused on immunometabolism.Frontiers in oncology · 2022Review
- EZH2: Its regulation and roles in immune disturbance of SLE.Frontiers in pharmacology · 2022Review
- EZH2 Promotes T Follicular Helper Cell Differentiation Through Enhancing STAT3 Phosphorylation in Patients With Primary Sjögren's Syndrome.Frontiers in immunology · 2022Article
- Ezh2 harnesses the intranuclear actin cytoskeleton to remodel chromatin in differentiating Th cells.iScience · 2021Article
- The Effects of Interferons on Allogeneic T Cell Response in GVHD: The Multifaced Biology and Epigenetic Regulations.Frontiers in immunology · 2021Review
- The Epigenetic Regulator EZH2 Instructs CD4 T Cell Response to Acute Viral Infection via Coupling of Cell Expansion and Metabolic Fitness.Journal of virology · 2020Article
- T-cell expression of Bruton's tyrosine kinase promotes autoreactive T-cell activation and exacerbates aplastic anemia.Cellular & molecular immunology · 2020Article
- The histone methyltransferase EZH2 primes the early differentiation of follicular helper T cells during acute viral infection.Cellular & molecular immunology · 2020Article
- The CD38/NAD/SIRTUIN1/EZH2 Axis Mitigates Cytotoxic CD8 T Cell Function and Identifies Patients with SLE Prone to Infections.Cell reports · 2020Article
- Continuous Developmental and Early Life Trichloroethylene Exposure Promoted DNA Methylation Alterations in Polycomb Protein Binding Sites in Effector/Memory CD4Frontiers in immunology · 2019Article
- Ezh2 programs TNature communications · 2018Article
- Epigenetic mechanisms of tumor resistance to immunotherapy.Cellular and molecular life sciences : CMLS · 2018Review
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
Acquired aplastic anemia (AA) is a potentially fatal bone marrow (BM) failure syndrome. IFN-γ-producing Th1 CD4(+) T cells mediate the immune destruction of hematopoietic cells, and they are central to the pathogenesis. However, the molecular events that control the development of BM-destructive Th1 cells remain largely unknown. Ezh2 is a chromatin-modifying enzyme that regulates multiple cellular processes primarily by silencing gene expression. We recently reported that Ezh2 is crucial for inflammatory T cell responses after allogeneic BM transplantation. To elucidate whether Ezh2 mediates pathogenic Th1 responses in AA and the mechanism of Ezh2 action in regulating Th1 cells, we studied the effects of Ezh2 inhibition in CD4(+) T cells using a mouse model of human AA. Conditionally deleting Ezh2 in mature T cells dramatically reduced the production of BM-destructive Th1 cells in vivo, decreased BM-infiltrating Th1 cells, and rescued mice from BM failure. Ezh2 inhibition resulted in significant decrease in the expression of Tbx21 and Stat4, which encode transcription factors T-bet and STAT4, respectively. Introduction of T-bet but not STAT4 into Ezh2-deficient T cells fully rescued their differentiation into Th1 cells mediating AA. Ezh2 bound to the Tbx21 promoter in Th1 cells and directly activated Tbx21 transcription. Unexpectedly, Ezh2 was also required to prevent proteasome-mediated degradation of T-bet protein in Th1 cells. Our results demonstrate that Ezh2 promotes the generation of BM-destructive Th1 cells through a mechanism of transcriptional and posttranscriptional regulation of T-bet. These results also highlight the therapeutic potential of Ezh2 inhibition in reducing AA and other autoimmune diseases.
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