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Systemic inflammation commonly results from dysregulated activation of innate immune cells, and therapeutic targeting of the IL-1\u03b2 pathway has been used to ameliorate some of these diseases. Some hyperinflammatory syndromes, however, such as hemophagocytic lymphohistiocytosis and the newly classified proteasome disability syndromes, are refractory to such treatments, suggesting that other factors or environmental stressors may be contributing. In comparing two cytokine reporter mouse strains, we identify IFN-\u03b3 as a mediator of systemic autoinflammatory disease. Chronically elevated levels of IFN-\u03b3 resulted in progressive multiorgan inflammation and two copies of the mutant allele resulted in increased mortality accompanied by myeloproliferative disease. Disease was alleviated by genetic deletion of T-bet. These studies raise the possibility that therapeutics targeting the IFN-\u03b3 pathway might be effective in hyperinflammatory conditions refractory to IL-1\u03b2\u2013targeted therapies.<\/jats:p>","DOI":"10.4049\/jimmunol.1401992","type":"journal-article","created":{"date-parts":[[2015,1,31]],"date-time":"2015-01-31T00:17:48Z","timestamp":1422663468000},"page":"2358-2368","source":"Crossref","is-referenced-by-count":77,"title":["A Novel Model for IFN-\u03b3\u2013Mediated Autoinflammatory Syndromes"],"prefix":"10.1093","volume":"194","author":[{"given":"R Lee","family":"Reinhardt","sequence":"first","affiliation":[{"name":"Howard Hughes Medical Institute, University of California San Francisco , San Francisco, CA 94143"},{"name":"Department of Medicine, University of California San Francisco , San Francisco, CA 94143"},{"name":"Department of Microbiology and Immunology, University of California San Francisco , San Francisco, CA 94143"},{"name":"Department of Immunology, Duke University Medical Center , Durham, NC 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Erh","family":"Liang","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, University of California San Francisco , San Francisco, CA 94143"},{"name":"Department of Medicine, University of California San Francisco , San Francisco, CA 94143"},{"name":"Department of Microbiology and Immunology, University of California San Francisco , San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Bao","sequence":"additional","affiliation":[{"name":"Department of Immunology, Duke University Medical Center , Durham, NC 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"April E","family":"Price","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, University of California San Francisco , San Francisco, CA 94143"},{"name":"Department of Medicine, University of California San Francisco , San Francisco, CA 94143"},{"name":"Department of Microbiology and Immunology, University of California San Francisco , San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Mohrs","sequence":"additional","affiliation":[{"name":"Trudeau Institute , Saranac Lake, NY 12983"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben L","family":"Kelly","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center , New Orleans, LA 70112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard M","family":"Locksley","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, University of California San Francisco , San Francisco, CA 94143"},{"name":"Department of Medicine, University of California San Francisco , San Francisco, CA 94143"},{"name":"Department of Microbiology and Immunology, University of California San Francisco , San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,3,1]]},"reference":[{"key":"2025030705130356700_r1","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1146\/annurev.immunol.25.022106.141627","article-title":"Horror autoinflammaticus: the molecular pathophysiology of autoinflammatory disease","volume":"27","author":"Masters","year":"2009","journal-title":"Annu. 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