ArticleBlood2012
Inhibition of histone methylation arrests ongoing graft-versus-host disease in mice by selectively inducing apoptosis of alloreactive effector T cells.
Article in Blood, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 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.
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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
49 citing papers in PubMed, 65 citations in OpenAlex.
- Epigenetic regulation in transplant rejection and tolerance: mechanisms and therapeutic prospects.Frontiers in cardiovascular medicine · 2026Review
- Nuclear-localized metabolic enzymes: emerging key players in tumor epigenetic regulation.Molecular and cellular biochemistry · 2025Review
- Impact of Novel Agents on Allogeneic Hematopoietic Cell Transplantation in Patients with T-Cell Lymphomas.Cells · 2025Review
- Mechanisms and Therapeutic Implications of EZH2 in Nasal Diseases.Clinical reviews in allergy & immunology · 2025Review
- Infection and inflammation stimulate expansion of a CD74The EMBO journal · 2023Article
- The impact of epigenetic modifications on allogeneic hematopoietic stem cell transplantation.Frontiers in immunology · 2023Review
- Epigenetics in lymphocyte and lymphoma: EZH2 as an easy-to-access therapeutic target?International journal of hematology · 2022Article
- The pleiotropic roles of EZH2 in T-cell immunity and immunotherapy.International journal of hematology · 2022Review
- Polycomb Directed Cell Fate Decisions in Development and Cancer.Epigenomes · 2022Review
- Integrated Multiomic Profiling Identifies the Epigenetic Regulator PRC2 as a Therapeutic Target to Counteract Leukemia Immune Escape and Relapse.Cancer discovery · 2022Article
- Low-Dose 5-Aza and DZnep Alleviate Acute Graft-Frontiers in immunology · 2022Article
- New hope offered to reduce GVHD.Blood · 2021Article
- Graft-versus-host disease depletes plasmacytoid dendritic cell progenitors to impair tolerance induction.The Journal of clinical investigation · 2021Article
- Histone Methyltransferase EZH2: A Potential Therapeutic Target for Kidney Diseases.Frontiers in physiology · 2021Review
- EZH2 Inhibition Compromises α4-1BB-Mediated Antitumor Efficacy by Reducing the Survival and Effector Programming of CD8Frontiers in immunology · 2021Article
- The Promise for Histone Methyltransferase Inhibitors for Epigenetic Therapy in Clinical Oncology: A Narrative Review.Advances in therapy · 2020Review
- Ezh2-mediated epigenetic modification is required for allogeneic T cell-induced lupus disease.Arthritis research & therapy · 2020Article
- EZH2 as a Regulator of CD8+ T Cell Fate and Function.Frontiers in immunology · 2020Review
- Histone Methylation Inhibitor DZNep Ameliorated the Renal Ischemia-Reperfusion InjuryFrontiers in medicine · 2020Article
- Epigenetic reprogramming of immune cells in injury, repair, and resolution.The Journal of clinical investigation · 2019Review
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
Abstract
Histone methylation is thought to be important for regulating Ag-driven T-cell responses. However, little is known about the effect of modulating histone methylation on inflammatory T-cell responses. We demonstrate that in vivo administration of the histone methylation inhibitor 3-deazaneplanocin A (DZNep) arrests ongoing GVHD in mice after allogeneic BM transplantation. DZNep caused selective apoptosis in alloantigen-activated T cells mediating host tissue injury. This effect was associated with the ability of DZNep to selectively reduce trimethylation of histone H3 lysine 27, deplete the histone methyltransferase Ezh2 specific to trimethylation of histone H3 lysine 27, and activate proapoptotic gene Bim repressed by Ezh2 in antigenic-activated T cells. In contrast, DZNep did not affect the survival of alloantigen-unresponsive T cells in vivo and naive T cells stimulated by IL-2 or IL-7 in vitro. Importantly, inhibition of histone methylation by DZNep treatment in vivo preserved the antileukemia activity of donor T cells and did not impair the recovery of hematopoiesis and lymphocytes, leading to significantly improved survival of recipients after allogeneic BM transplantation. Our findings indicate that modulation of histone methylation may have significant implications in the development of novel approaches to treat ongoing GVHD and other T cell-mediated inflammatory disorders in a broad context.
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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.