The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
Cutting Edge: cGAS Is Required for Lethal Autoimmune Disease in the Trex1-Deficient Mouse Model of Aicardi–Goutières Syndrome
Open accessAbstract
Detection of intracellular DNA triggers activation of the stimulator of IFN genes–dependent IFN-stimulatory DNA (ISD) pathway, which is essential for antiviral immune responses. However, chronic activation of this pathway is implicated in autoimmunity. Mutations in TREX1, a 3′ repair exonuclease that degrades cytosolic DNA, cause Aicardi–Goutières syndrome and chilblain lupus. Trex1−/− mice develop lethal, IFN-driven autoimmune disease that is dependent on activation of the ISD pathway, but the DNA sensors that detect the endogenous DNA that accumulates in Trex1−/− mice have not been defined. Multiple DNA sensors have been proposed to activate the ISD pathway, including cyclic GMP–AMP synthase (cGAS). In this study, we show that Trex1−/− mice lacking cGAS are completely protected from lethality, exhibit dramatically reduced tissue inflammation, and fail to develop autoantibodies. These findings implicate cGAS as a key driver of autoimmune disease and suggest that cGAS inhibitors may be useful therapeutics for Aicardi–Goutières syndrome and related autoimmune diseases.
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Cites
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
Lee-Kirsch, M. A., Gong, M., Chowdhury, D., Senenko, L., Engel, K., Lee, Y.-A., de Silva, U., Bailey, S. L., Witte, T., Vyse, T. J., et al. (2007) · Nature Genetics · doi:10.1038/ng2091 · Cited by 730
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Lahaye, X., Satoh, T., Gentili, M., Cerboni, S., Conrad, C., Hurbain, I., El Marjou, A., Lacabaratz, C., Lelièvre, J.-D., & Manel, N. (2013) · Immunity · doi:10.1016/j.immuni.2013.11.002 · Cited by 390
Human Cytomegalovirus Tegument Protein pUL83 Inhibits IFI16-Mediated DNA Sensing for Immune Evasion
Li, T., Chen, J., & Cristea, I. M. (2013) · Cell Host & Microbe · doi:10.1016/j.chom.2013.10.007 · Cited by 226
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
The 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
Hopfner, K.-P., & Hornung, V. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0244-x · Cited by 2,052
DNA sensing by the cGAS–STING pathway in health and disease
Motwani, M., Pesiridis, S., & Fitzgerald, K. A. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-019-0151-1 · Cited by 1,467
The cGAS–cGAMP–STING pathway connects DNA damage to inflammation, senescence, and cancer
Li, T., & Chen, Z. J. (2018) · Journal of Experimental Medicine · doi:10.1084/jem.20180139 · Cited by 1,293
Metadata
- Authors
- Gray, E. E., Treuting, P. M., Woodward, J. J., & Stetson, D. B.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-09-01
- Volume
- 195
- Issue
- 5
- Pages
- 1939-1943
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1857174086
- Cited by
- 384
- References
- 6
- FWCI
- 13.74
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Gray, E. E., Treuting, P. M., Woodward, J. J., & Stetson, D. B. (2015). Cutting Edge: cGAS Is Required for Lethal Autoimmune Disease in the Trex1-Deficient Mouse Model of Aicardi–Goutières Syndrome. The Journal of Immunology. https://doi.org/10.4049/jimmunol.1500969
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