G3BP1 Inhibition Alleviates Intracellular Nucleic Acid-Induced Autoimmune Responses.
J Immunol
; 206(10): 2453-2467, 2021 05 15.
Article
em En
| MEDLINE
| ID: mdl-33941659
ABSTRACT
The detection of intracellular nucleic acids is a fundamental mechanism of host defense against infections. The dysregulated nucleic acid sensing, however, is a major cause for a number of autoimmune diseases. In this study, we report that GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) is critical for both intracellular DNA- and RNA-induced immune responses. We found that in both human and mouse cells, the deletion of G3BP1 led to the dampened cGAS activation by DNA and the insufficient binding of RNA by RIG-I. We further found that resveratrol (RSVL), a natural compound found in grape skin, suppressed both intracellular DNA- and RNA-induced type I IFN production through inhibiting G3BP1. Importantly, using experimental mouse models for Aicardi-Goutières syndrome, an autoimmune disorder found in humans, we demonstrated that RSVL effectively alleviated intracellular nucleic acid-stimulated autoimmune responses. Thus, our study demonstrated a broader role of G3BP1 in sensing different kinds of intracellular nucleic acids and presented RSVL as a potential treatment for autoimmune conditions caused by dysregulated nucleic acid sensing.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Ácidos Nucleicos
/
Transdução de Sinais
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Autoimunidade
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DNA Helicases
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RNA Helicases
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Espaço Intracelular
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Proteínas com Motivo de Reconhecimento de RNA
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Proteínas de Ligação a Poli-ADP-Ribose
Limite:
Animals
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Humans
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China