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In this study, we show that CASP8 negatively regulates retinoic acid\u2013inducible gene I (RIG-I) signaling such that, in its absence, stimulation of the RIG-I pathway in dendritic cells (DCs) produced modestly enhanced activation of IFN regulatory factor 3 with correspondingly greater amounts of proinflammatory cytokines. In addition, mice lacking DC-specific CASP8 (dcCasp8\u2212\/\u2212 mice) develop age-dependent symptoms of autoimmune disease characterized by hyperactive DCs and T cells, spleen and liver immunopathology, and the appearance of Th1-polarized CD4+ T cells. Such mice infected with chronic lymphocytic choriomeningitis virus, an RNA virus detected by RIG-I, mounted an enhanced lymphocytic choriomeningitis virus\u2013specific immune response as measured by increased proportions of Ag-specific CD4+ T cells and multicytokine-producing CD4+ and CD8+ T cells. These results show that CASP8 subtly modulates DC maturation, which controls the spontaneous appearance of autoimmune T cells while simultaneously attenuating the acquired immune system and its potential to control a persistent viral infection.<\/jats:p>","DOI":"10.4049\/jimmunol.1601870","type":"journal-article","created":{"date-parts":[[2018,1,8]],"date-time":"2018-01-08T15:30:53Z","timestamp":1515425453000},"page":"1335-1346","source":"Crossref","is-referenced-by-count":4,"title":["The Effects of Dendritic Cell Hypersensitivity on Persistent Viral Infection"],"prefix":"10.1093","volume":"200","author":[{"given":"Jennifer S","family":"Tsau","sequence":"first","affiliation":[{"name":"Division of Biological Sciences, Molecular Biology Section, University of California , San Diego, La Jolla, CA 92093"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8935-5187","authenticated-orcid":false,"given":"Xin","family":"Huang","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Medicine, University of California , San Diego, La Jolla, CA 92093"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen-Yen","family":"Lai","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Medicine, University of California , San Diego, La Jolla, CA 92093"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen M","family":"Hedrick","sequence":"additional","affiliation":[{"name":"Division of Biological Sciences, Molecular Biology Section, University of California , San Diego, La Jolla, CA 92093"},{"name":"Cellular and Molecular Medicine, University of California , San Diego, La Jolla, CA 92093"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2018,2,15]]},"reference":[{"key":"2025030610020272600_r1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1146\/annurev-immunol-100311-102839","article-title":"Decisions about dendritic cells: past, present, and future","volume":"30","author":"Steinman","year":"2012","journal-title":"Annu. 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