Regulation of cGAS–STING signalling and its diversity of cellular outcomes
Abstract
The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signalling pathway, which recognizes both pathogen DNA and host-derived DNA, has emerged as a crucial component of the innate immune system, having important roles in antimicrobial defence, inflammatory disease, ageing, autoimmunity and cancer. Recent work suggests that the regulation of cGAS-STING signalling is complex and sophisticated. In this Review, we describe recent insights from structural studies that have helped to elucidate the molecular mechanisms of the cGAS-STING signalling cascade and we discuss how the cGAS-STING pathway is regulated by both activating and inhibitory factors. Furthermore, we summarize the newly emerging understanding of crosstalk between cGAS-STING signalling and other signalling pathways and provide examples to highlight the wide variety of cellular processes in which cGAS-STING signalling is involved, including autophagy, metabolism, ageing, inflammation and tumorigenesis.
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The cGAS-STING pathway recognizes mitochondrial DNA released during liver injury, leading to its activation and triggering inflammation with production of type I interferons and proinflammatory cytokines, which exacerbates liver inflammation and hepatocyte damage.
“It can recognize mtDNA released during liver injury, leading to its activation and the triggering of inflammation with the production of type I interferons (IFNs) and proinflammatory cytokines, which exacerbates liver inflammation and hepatocyte damage (20–22).”
From Matrix mechanical remodeled carrier-free nanosystem for programmable closed-loop reversal of liver fibrosis via STING alkylation (2025) · cites this paper as [21]
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References 279 · Cited by 287
- Authors
- Zhang, Z., & Zhang, C.
- Affiliations
- Center for Life Sciences (CN)
- Shanxi Medical University (CN)
- Corresponding author
- Zhang, Conggang
- Venue
- Nature Reviews Immunology
- Published
- 2025-01-07
- Volume
- 25
- Issue
- 6
- Pages
- 425-444
- ISSN
- 1474-1733 (ISSN-L)
- 1474-1741
- OpenAlex
- W4406116744
- Cited by
- 287
- References
- 279
- Citations by year
- 2026: 203 · 2025: 84
- FWCI
- 25.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature reviews. Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- cGAS, STING, innate immunity, DNA sensing, host DNA, signaling crosstalk, autophagy, metabolism, aging, inflammation, carcinogenesis, autoimmunity, interferon signaling, structural mechanisms
- MeSH terms
- STING Protein, Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase, Aging, Animals, Autophagy, Humans, Immunity, Innate, Inflammation, Membrane Proteins, Neoplasms, Nucleotidyltransferases, Signal Transduction
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