G3BP1 Inhibition Alleviates Intracellular Nucleic Acid–Induced Autoimmune Responses
| Autor: | Qiu-Ying Han, Yuan Chen, Li Ailing, Na Wang, Zeng-Lin Guo, Tao Zhou, Zhao-Shan Liu, Kun He, Hong Cai, Tao Li, Jiang-Man Zhao, Xue-Min Zhang, Feng Zhang, Tian Xia, Liang Chen, Wen Xue, Jie Mao, Weihua Li, Xin Liu, Li-Ming Sun |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Cell Survival
Immunology Intracellular Space Autoimmunity Autoimmune responses Resveratrol Transfection Gene Knockout Techniques Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Immune system Nucleic Acids Animals Humans Immunology and Allergy Poly-ADP-Ribose Binding Proteins Mice Knockout Mice Inbred BALB C Macrophages DNA Helicases Type I IFN production RNA Fibroblasts Cell biology Mice Inbred C57BL HEK293 Cells RNA Recognition Motif Proteins chemistry A549 Cells Nucleic acid RNA Helicases Intracellular DNA Signal Transduction 030215 immunology |
| Zdroj: | The Journal of Immunology. 206:2453-2467 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.2001111 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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