| First Author | Gray EE | Year | 2015 |
| Journal | J Immunol | Volume | 195 |
| Issue | 5 | Pages | 1939-43 |
| PubMed ID | 26223655 | Mgi Jnum | J:236438 |
| Mgi Id | MGI:5806049 | Doi | 10.4049/jimmunol.1500969 |
| Citation | Gray EE, et al. (2015) Cutting Edge: cGAS Is Required for Lethal Autoimmune Disease in the Trex1-Deficient Mouse Model of Aicardi-Goutieres Syndrome. J Immunol 195(5):1939-43 |
| abstractText | 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-Goutieres 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-Goutieres syndrome and related autoimmune diseases. |
