Nuclear PCGF3 inhibits the antiviral immune response by suppressing the interferon-stimulated gene.

IF 6.1 2区生物学 Q1 CELL BIOLOGY

Cell Death Discovery Pub Date : 2024-10-05 DOI:10.1038/s41420-024-02194-x

Gula Da, Junmin Wang, Jing Shang, Cuiping Xun, Yang Yu, Yong Wang, Ning Tie, Hongbin Li

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Abstract

Type I interferon (IFN-I) plays a crucial role in the antiviral immune response and inflammatory autoimmune diseases by inducing the expression of IFN-stimulated genes (ISGs). Hence, the regulation of ISG expression is fundamental for maintaining immune homeostasis. In this study, we found that PCGF3 negatively regulates the antiviral response by suppressing the expression of ISGs. The deficiency of PCGF3 in innate immune cells results in an augmented expression of ISGs in response to IFN-I stimulation. Mechanistically, PCGF3 is recruited to interferon-stimulated response elements (ISREs) region in an IFN-dependent way, precluding STAT1 from binding to the ISG promoter and diminishing ISRE activity. Additionally, we observed a negative correlation between decreased PCGF3 expression and elevated ISG expression in peripheral blood mononuclear cells (PBMCs) of patients with dermatomyositis (DM). Our findings clarified the epigenetic regulatory role of PCGF3 in inhibiting the excessive expression of ISGs induced by IFN-I under pathological circumstances.

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核 PCGF3 通过抑制干扰素刺激基因来抑制抗病毒免疫反应。

I 型干扰素（IFN-I）通过诱导 IFN 刺激基因（ISGs）的表达，在抗病毒免疫反应和炎症性自身免疫疾病中发挥着至关重要的作用。因此，调控 ISG 的表达是维持免疫平衡的基础。在这项研究中，我们发现 PCGF3 通过抑制 ISGs 的表达来负向调节抗病毒反应。先天性免疫细胞中 PCGF3 的缺乏会导致 IFN-I 刺激下 ISGs 的表达增加。从机理上讲，PCGF3 以一种依赖于 IFN 的方式被招募到干扰素刺激反应元件（ISREs）区域，阻止 STAT1 与 ISG 启动子结合并降低 ISRE 的活性。此外，我们还观察到皮肌炎（DM）患者外周血单核细胞（PBMC）中 PCGF3 表达减少与 ISG 表达升高之间存在负相关。我们的研究结果阐明了 PCGF3 在病理情况下抑制 IFN-I 诱导的 ISGs 过度表达的表观遗传调控作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Death Discovery Biochemistry, Genetics and Molecular Biology-Cell Biology

CiteScore

8.30

自引率

1.40%

发文量

468

审稿时长

9 weeks

期刊介绍： Cell Death Discovery is a multidisciplinary, international, online-only, open access journal, dedicated to publishing research at the intersection of medicine with biochemistry, pharmacology, immunology, cell biology and cell death, provided it is scientifically sound. The unrestricted access to research findings in Cell Death Discovery will foster a dynamic and highly productive dialogue between basic scientists and clinicians, as well as researchers in industry with a focus on cancer, neurobiology and inflammation research. As an official journal of the Cell Death Differentiation Association (ADMC), Cell Death Discovery will build upon the success of Cell Death & Differentiation and Cell Death & Disease in publishing important peer-reviewed original research, timely reviews and editorial commentary. Cell Death Discovery is committed to increasing the reproducibility of research. To this end, in conjunction with its sister journals Cell Death & Differentiation and Cell Death & Disease, Cell Death Discovery provides a unique forum for scientists as well as clinicians and members of the pharmaceutical and biotechnical industry. It is committed to the rapid publication of high quality original papers that relate to these subjects, together with topical, usually solicited, reviews, editorial correspondence and occasional commentaries on controversial and scientifically informative issues.