cGAS in action: Expanding roles in immunity and inflammation
Open accessAbstract
cGAS sensing of DNA: A comprehensive look: The immune system uses the cGAS-STING (cyclic GMP-AMP synthase–stimulator of interferon genes) signaling pathway to detect the presence of intracellular DNA. This is beneficial because cytosolic DNA is often a sign of host damage or invasion by pathogens. However, inappropriate responses to self-DNA must be suppressed to prevent detrimental effects on the host. Ablasser and Chen review the latest advances uncovering how cGAS and STING control inflammatory responses and are themselves regulated. Special attention is paid to the role of cGAS in sterile inflammatory conditions as well as to the therapeutic potential of modulating this pathway. Science , this issue p. eaat8657
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The cGAS-STING signalling pathway mediates immune sensing of DNA.
“Here we show that the cGAS–STING signalling pathway, which mediates immune sensing of DNA3, is a critical driver of chronic inflammation and functional decline during ageing.”
From cGAS–STING drives ageing-related inflammation and neurodegeneration (2023) · cites this paper as [3]
cGAS catalyzes production of the second messenger cGMP that binds STING, resulting in phosphorylation of IRF3 and NF-κB and stimulating production of type I interferons and inflammatory cytokines.
“cGAS catalyzes the production of the second messenger cGMP that binds to stimulator of interferon genes (STING). This results in the phosphorylation of both interferon-regulatory factor 3 (IRF3) and of NF-κB transcription factors, thereby stimulating respectively the production of type I interferons and inflammatory cytokines [171,172,173,174].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [174]
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- Authors
- Ablasser, A., & Chen, Z. J.
- Affiliations
- École Polytechnique Fédérale de Lausanne (CH)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Ablasser, Andrea
- Chen, Zhijian J.
- Venue
- Science
- Published
- 2019-03-08
- Volume
- 363
- Issue
- 6431
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2921875691
- Semantic Scholar
- 69a7b3140004c4b312c5049945d8798bcc24ab85
- Cited by
- 1,077
- References
- 19
- Citations by year
- 2026: 152 · 2025: 189 · 2024: 182 · 2023: 167 · 2022: 138 · 2021: 108 · 2020: 99 · 2019: 41
- FWCI
- 8.34
- Type
- journal article
- Language
- en
- Open access
- green
- infoscience.epfl.ch
- Licence
- cc-by-nc-nd
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Funders
- Lupus Research Alliance
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- National Institutes of Health
- National Cancer Institute (U01CA218422)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (P50AR070594)
- 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 › Inflammasome and immune disorders
- Keywords
- cGAS, STING, cGAS-STING pathway, damage-associated molecular patterns, pathogen-associated molecular patterns, sterile inflammation, innate immunity, inflammation regulation, anti-inflammatory therapy
- MeSH terms
- STING Protein, Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase, Cell Compartmentation, DNA, Enzyme Activation, Humans, Immunity, Inflammation, Membrane Proteins, Nucleotidyltransferases
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