The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Activation of cyclic GMP-AMP synthase by self-DNA causes autoimmune diseases
Open accessAbstract
Significance: The immune system detects microbial DNA in the cytosol of infected cells and mounts effective antimicrobial responses, including the production of type-I interferons. However, when self-DNA enters or accumulates in the cytosol, it can cause autoimmune diseases. Mutations of the exonuclease Trex1 in humans have been linked to autoimmune diseases including Aicardi–Goutieres Syndrome (AGS) and systemic lupus erythematosus (SLE). In mice, genetic deletion of Trex1 or the lysosomal nuclease DNaseII leads to lethal autoimmune diseases. Here we show that cyclic GMP-AMP synthase (cGAS) activation by self-DNA is responsible for the lethal autoimmune diseases in these models. These results provide the proof-of-concept that inhibition of cGAS may be an effective therapy for some autoimmune diseases such as AGS and SLE.
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Cites
Cyclic GMP-AMP Synthase Is a Cytosolic DNA Sensor That Activates the Type I Interferon Pathway
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Self-citationSTING is an endoplasmic reticulum adaptor that facilitates innate immune signalling
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CGAS produces a 2′-5′-linked cyclic dinucleotide second messenger that activates STING.
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Pan-viral specificity of IFN-induced genes reveals new roles for cGAS in innate immunity
Schoggins, J. W., MacDuff, D. A., Imanaka, N., Gainey, M. D., Shrestha, B., Eitson, J. L., Mar, K. B., Richardson, R. B., Ratushny, A. V., Litvak, V., et al. (2014) · Nature · doi:10.1038/nature12862 · Cited by 896
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Cited by
Regulation and function of the cGAS–STING pathway of cytosolic DNA sensing
Chen, Q., Sun, L., & Chen, Z. J. (2016) · Nature Immunology · doi:10.1038/ni.3558 · Cited by 2,333
Self-citationThe cGAS–STING pathway as a therapeutic target in inflammatory diseases
Decout, A., Katz, J. D., Venkatraman, S., & Ablasser, A. (2021) · Nature Reviews Immunology · doi:10.1038/s41577-021-00524-z · Cited by 2,309
Molecular mechanisms and cellular functions of cGAS–STING signalling
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cGAS surveillance of micronuclei links genome instability to innate immunity
Mackenzie, K. J., Carroll, P., Martin, C.-A., Murina, O., Fluteau, A., Simpson, D. J., Olova, N., Sutcliffe, H., Rainger, J. K., Leitch, A., et al. (2017) · Nature · doi:10.1038/nature23449 · Cited by 1,752
DAMP-sensing receptors in sterile inflammation and inflammatory diseases
Gong, T., Liu, L., Jiang, W., & Zhou, R. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-019-0215-7 · Cited by 1,672
Metadata
- Authors
- Gao, D., Li, T., Li, X.-D., Chen, X., Li, Q.-Z., Wight-Carter, M., & Chen, Z. J.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2015-09-14
- Volume
- 112
- Issue
- 42
- Pages
- E5699-705
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2147701649
- Cited by
- 685
- References
- 9
- FWCI
- 19.24
- Type
- journal article
- Language
- en
- Open access
- green
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