Journal
JOURNAL OF IMMUNOLOGY
Volume 206, Issue 10, Pages 2453-2467Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.2001111
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Funding
- National Key Research and Development Program of China [2020YFA0707702, 2020YFA0707703]
- China National Natural Science Foundation [81925017, 81672734]
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The study demonstrates the critical role of G3BP1 in immune responses induced by intracellular DNA and RNA, as its deletion leads to impaired cGAS activation and insufficient binding of RNA by RIG-I. Resveratrol suppresses type I IFN production by inhibiting G3BP1 and effectively alleviates intracellular nucleic acid-stimulated autoimmune responses in experimental mouse models for Aicardi-Goutières syndrome.
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-Gouti-eres 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.
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