{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T15:56:29Z","timestamp":1790092589074,"version":"4.0.1"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2007,9,1]],"date-time":"2007-09-01T00:00:00Z","timestamp":1188604800000},"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":[[2007,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Psoriasis is an inflammatory skin disease, onset and severity of which are controlled by multiple genetic factors; aberrant expression of and responses to several cytokines including IFN-\u03b1\/IFN-\u03b2 and IFN-\u03b3 are associated with this \u201ctype 1\u201d disease. However, it remains unclear whether genetic regulation influences these cytokine-related abnormalities. Mice deficient for IFN regulatory factor-2 (IRF-2) on the C57BL\/6 background (IRF-2\u2212\/\u2212BN mice) exhibited accelerated IFN-\u03b1\/IFN-\u03b2 responses leading to a psoriasis-like skin inflammation. In this study, we found that this skin phenotype disappeared in IRF-2\u2212\/\u2212 mice with the BALB\/c or BALB\/c \u00d7 C57BL\/6 F1 backgrounds. Genome-wide scan revealed two major quantitative trait loci controlled the skin disease severity. Interestingly, these loci were different from that for the defect in CD4+ dendritic cells, another IFN-\u03b1\/IFN-\u03b2-dependent phenotype of the mice. Notably, IFN-\u03b3 expression as well as spontaneous IFN-\u03b1\/IFN-\u03b2 responses were up-regulated several fold spontaneously in the skin in IRF-2\u2212\/\u2212BN mice but not in IRF-2\u2212\/\u2212 mice with \u201cresistant\u201d backgrounds. The absence of such IFN-\u03b3 up-regulation in IRF-2\u2212\/\u2212BN mice lacking the IFN-\u03b1\/IFN-\u03b2 receptor or \u03b22-microglobulin indicated that accelerated IFN-\u03b1\/IFN-\u03b2 signals augmented IFN-\u03b3 expression by CD8+ T cells in the skin. IFN-\u03b3 indeed played pathogenic roles as skin inflammation was delayed and was much more infrequent when IRF-2\u2212\/\u2212BN mice lacked the IFN-\u03b3 receptor. Our current study thus revealed a novel genetic mechanism that kept the skin immune system under control and prevented skin inflammation through regulating the magnitude of IFN-\u03b1\/IFN-\u03b2 responses and downstream IFN-\u03b3 production, independently of CD4+ dendritic cells.<\/jats:p>","DOI":"10.4049\/jimmunol.179.5.3249","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:17:46Z","timestamp":1397848666000},"page":"3249-3257","source":"Crossref","is-referenced-by-count":21,"title":["Genetic Control Directed toward Spontaneous IFN-\u03b1\/IFN-\u03b2 Responses and Downstream IFN-\u03b3 Expression Influences the Pathogenesis of a Murine Psoriasis-Like Skin Disease"],"prefix":"10.1093","volume":"179","author":[{"given":"Fuyuko","family":"Arakura","sequence":"first","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Graduate School of Medicine, Shinshu University , Matsumoto ,","place":["Japan"]},{"name":"Department of Dermatology, School of Medicine, Shinshu University , Matsumoto ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeaki","family":"Hida","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Graduate School of Medicine, Shinshu University , Matsumoto ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eri","family":"Ichikawa","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Graduate School of Medicine, Shinshu University , Matsumoto ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chihiro","family":"Yajima","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Graduate School of Medicine, Shinshu University , Matsumoto ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinsuke","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Graduate School of Medicine, Shinshu University , Matsumoto ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiaki","family":"Saida","sequence":"additional","affiliation":[{"name":"Department of Dermatology, School of Medicine, Shinshu University , Matsumoto ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinsuke","family":"Taki","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Graduate School of Medicine, Shinshu University , Matsumoto ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2007,9,1]]},"reference":[{"key":"2026012809350292300_R1","first-page":"R43","volume-title":"Hum. 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