{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T21:37:59Z","timestamp":1792013879556,"version":"4.4.0"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Detection of intracellular DNA triggers activation of the stimulator of IFN genes\u2013dependent 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\u2032 repair exonuclease that degrades cytosolic DNA, cause Aicardi\u2013Gouti\u00e8res syndrome and chilblain lupus. Trex1\u2212\/\u2212 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\u2212\/\u2212 mice have not been defined. Multiple DNA sensors have been proposed to activate the ISD pathway, including cyclic GMP\u2013AMP synthase (cGAS). In this study, we show that Trex1\u2212\/\u2212 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\u2013Gouti\u00e8res syndrome and related autoimmune diseases.<\/jats:p>","DOI":"10.4049\/jimmunol.1500969","type":"journal-article","created":{"date-parts":[[2015,7,29]],"date-time":"2015-07-29T22:36:30Z","timestamp":1438209390000},"page":"1939-1943","source":"Crossref","is-referenced-by-count":378,"title":["Cutting Edge: cGAS Is Required for Lethal Autoimmune Disease in the Trex1-Deficient Mouse Model of Aicardi\u2013Gouti\u00e8res Syndrome"],"prefix":"10.1093","volume":"195","author":[{"given":"Elizabeth E","family":"Gray","sequence":"first","affiliation":[{"name":"Department of Immunology, University of Washington School of Medicine , Seattle, WA 98195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piper M","family":"Treuting","sequence":"additional","affiliation":[{"name":"Department of Comparative Medicine, University of Washington School of Medicine , Seattle, WA 98195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua J","family":"Woodward","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Washington School of Medicine , Seattle, WA 98195"},{"name":"Department of Bioengineering, University of Washington School of Medicine , Seattle, WA 98195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel B","family":"Stetson","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Washington School of Medicine , Seattle, WA 98195"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,9,1]]},"reference":[{"key":"2025030704091613100_r1","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1146\/annurev-immunol-032713-120156","article-title":"Innate immune sensing and signaling of cytosolic nucleic acids","volume":"32","author":"Wu","year":"2014","journal-title":"Annu. 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