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激活 EZH2 以增加调节性 T 细胞中的 H3K27me3 水平，通过驱动早期效应器分化来增强免疫抑制。

Hyperactivating EZH2 to augment H3K27me3 levels in regulatory T cells enhances immune suppression by driving early effector differentiation.

机构信息

Division of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.

Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO 80045, USA; RNA Bioscience Initiative, University of Colorado School of Medicine, Aurora, CO 80045, USA.

出版信息

Cell Rep. 2024 Sep 24;43(9):114724. doi: 10.1016/j.celrep.2024.114724. Epub 2024 Sep 11.

DOI:10.1016/j.celrep.2024.114724
PMID:39264807
Abstract

The immunosuppressive function of regulatory T (Treg) cells is essential for maintaining immune homeostasis. Enhancer of zeste homolog 2 (EZH2), a histone H3 lysine 27 (H3K27) methyltransferase, plays a key role in maintaining Treg cell function upon CD28 co-stimulation, and Ezh2 deletion in Treg cells causes autoimmunity. Here, we assess whether increasing H3K27me3 levels, by using an Ezh2 gain-of-function mutation, will improve Treg cell function. We find that Treg cells expressing Ezh2 display an effector Treg phenotype, are poised for improved homing to organ tissues, and can accelerate remission from autoimmunity. The H3K27me3 landscape and transcriptome of naive Ezh2 Treg cells exhibit a redistribution of H3K27me3 modifications that recapitulates the gene expression profile of activated Ezh2 Treg cells after CD28 co-stimulation. Altogether, increased H3K27me3 levels promote the differentiation of effector Treg cells that can better suppress autoimmunity.

摘要

调节性 T (Treg) 细胞的免疫抑制功能对于维持免疫稳态至关重要。增强子结合抑制因子 2 (EZH2) 是一种组蛋白 H3 赖氨酸 27 (H3K27) 甲基转移酶，在 CD28 共刺激下维持 Treg 细胞功能方面发挥着关键作用，而 Treg 细胞中 Ezh2 的缺失会导致自身免疫。在这里，我们评估了通过使用 Ezh2 功能获得性突变来增加 H3K27me3 水平是否会改善 Treg 细胞功能。我们发现，表达 Ezh2 的 Treg 细胞表现出效应性 Treg 表型，更倾向于向器官组织归巢，并且可以加速自身免疫的缓解。幼稚 Ezh2 Treg 细胞的 H3K27me3 图谱和转录组显示 H3K27me3 修饰的重新分布，再现了 CD28 共刺激后激活的 Ezh2 Treg 细胞的基因表达谱。总之，增加 H3K27me3 水平促进了效应性 Treg 细胞的分化，从而更好地抑制自身免疫。

相似文献

[1]
Hyperactivating EZH2 to augment H3K27me3 levels in regulatory T cells enhances immune suppression by driving early effector differentiation.

Cell Rep. 2024-9-24

[2]
Increased EZH2 function in regulatory T cells promotes their capacity to suppress autoimmunity by driving effector differentiation prior to activation.

bioRxiv. 2024-4-10

[3]
Disruption of FOXP3-EZH2 Interaction Represents a Pathobiological Mechanism in Intestinal Inflammation.

Cell Mol Gastroenterol Hepatol. 2018-9-14

[4]
The chromatin-modifying enzyme Ezh2 is critical for the maintenance of regulatory T cell identity after activation.

Immunity. 2015-2-17

[5]
Enhancer of zeste homolog 2-catalysed H3K27 trimethylation plays a key role in acute-on-chronic liver failure via TNF-mediated pathway.

Cell Death Dis. 2018-5-22

[6]
The Role of the Histone Methyltransferase Enhancer of Zeste Homolog 2 (EZH2) in the Pathobiological Mechanisms Underlying Inflammatory Bowel Disease (IBD).

J Biol Chem. 2017-1-13

[7]
EZH2 deficiency attenuates Treg differentiation in rheumatoid arthritis.

J Autoimmun. 2020-3

[8]
EZH2 W113C is a gain-of-function mutation in B-cell lymphoma enabling both PRC2 methyltransferase activation and tazemetostat resistance.

J Biol Chem. 2023-4

[9]
Humanized NOD/SCID/IL2rγ mice exhibit functionally augmented human regulatory T cells associated with enzymatic up-regulation of H3K27me3 in comparison with humans.

Clin Exp Immunol. 2021-5

[10]
The lysine methyltransferases SET and MYND domain containing 2 (Smyd2) and Enhancer of Zeste 2 (Ezh2) co-regulate osteoblast proliferation and mineralization.

Gene. 2023-1-30

引用本文的文献

[1]
Multi-Faceted Role of Histone Methyltransferase Enhancer of Zeste 2 (EZH2) in Neuroinflammation and Emerging Targeting Options.

Biology (Basel). 2025-6-23

[2]
CD28 and ICOS in immune regulation: Structural insights and therapeutic targeting.

Bioorg Med Chem Lett. 2025-6-15

[3]
Targeting EZH2 in autoimmune diseases: unraveling epigenetic regulation and therapeutic potential.

Naunyn Schmiedebergs Arch Pharmacol. 2025-4-8

[4]
The impact of cell states on heterochromatin dynamics.

Biochem J. 2024-11-6

本文引用的文献

[1]
Nucleation and spreading maintain Polycomb domains every cell cycle.

Cell Rep. 2024-4-23

[2]
CXCR3 expression in regulatory T cells drives interactions with type I dendritic cells in tumors to restrict CD8 T cell antitumor immunity.

Immunity. 2023-7-11

[3]
CD103 Regulates Dermal Regulatory T Cell Motility and Interactions with CD11c-Expressing Leukocytes to Control Skin Inflammation.

J Immunol. 2023-8-15

[4]
CD103 integrin identifies a high IL-10-producing FoxP3 regulatory T-cell population suppressing allergic airway inflammation.

Allergy. 2022-4

[5]
CUT&RUNTools 2.0: a pipeline for single-cell and bulk-level CUT&RUN and CUT&Tag data analysis.

Bioinformatics. 2021-12-22

[6]
The demethylase inhibitor GSK-J4 limits inflammatory colitis by promoting de novo synthesis of retinoic acid in dendritic cells.

Sci Rep. 2021-1-14

[7]
PD-1 restraint of regulatory T cell suppressive activity is critical for immune tolerance.

J Exp Med. 2021-1-4

[8]
Maintenance DNA methylation is essential for regulatory T cell development and stability of suppressive function.

J Clin Invest. 2020-12-1

[9]
The PD-1 expression balance between effector and regulatory T cells predicts the clinical efficacy of PD-1 blockade therapies.

Nat Immunol. 2020-11

[10]
Mutant EZH2 Induces a Pre-malignant Lymphoma Niche by Reprogramming the Immune Response.

Cancer Cell. 2020-5-11

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