2. Academic Validation
  3. Nuclear PCGF3 inhibits the antiviral immune response by suppressing the interferon-stimulated gene

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

  • Cell Death Discov. 2024 Oct 5;10(1):429. doi: 10.1038/s41420-024-02194-x.
Gula Da # 1 2,  Junmin Wang # 3,  Jing Shang 1 2,  Cuiping Xun 1 2,  Yang Yu 1 2,  Yong Wang 1 2,  Ning Tie 4 5,  Hongbin Li 6 7
Affiliations

Affiliations

  • 1 Department of Rheumatology and Immunology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China.
  • 2 Inner Mongolia Key Laboratory for Pathogenesis and Diagnosis of Rheumatic and Autoimmune Diseases, Hohhot, China.
  • 3 Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
  • 4 Department of Rheumatology and Immunology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China. tiening@yeah.net.
  • 5 Inner Mongolia Key Laboratory for Pathogenesis and Diagnosis of Rheumatic and Autoimmune Diseases, Hohhot, China. tiening@yeah.net.
  • 6 Department of Rheumatology and Immunology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China. lhbwb73@126.com.
  • 7 Inner Mongolia Key Laboratory for Pathogenesis and Diagnosis of Rheumatic and Autoimmune Diseases, Hohhot, China. lhbwb73@126.com.
  • # Contributed equally.
PMID: 39368978 DOI: 10.1038/s41420-024-02194-x
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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