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We report the spontaneous development of psoriasis-like skin lesions as an SMS-like symptom in transgenic mice harboring one of the RIG-I SMS variants, E373A. Histological analysis revealed typical characteristics of psoriasis, including the abnormal proliferation and differentiation of keratinocytes leading to epidermal hyperplasia, and infiltrates consisting of neutrophils, dendritic cells and T cells. Levels of the IL-23\/IL-17 immune axis cytokines were high in the skin lesions. Rag2\u2212\/\u2212 transgenic mice showed partial amelioration of the phenotype, with down-regulation of inflammatory cytokines, including IL-17A, suggesting the importance of lymphocytes for the pathogenesis similar to that of human psoriasis. Of note, IL-17A deficiency abolished the skin phenotype, and treatment using the JAK inhibitor tofacitinib not only prevented onset, but also improved the skin manifestations even after onset. Our study provides further evidence for the involvement of RIG-I activation in the onset and progression of psoriasis via type I interferon signaling and the IL-23\/IL-17 axis.<\/jats:p>","DOI":"10.1093\/intimm\/dxaa071","type":"journal-article","created":{"date-parts":[[2020,10,28]],"date-time":"2020-10-28T08:12:00Z","timestamp":1603872720000},"page":"211-224","source":"Crossref","is-referenced-by-count":13,"title":["Psoriasis-like skin disorder in transgenic mice expressing a RIG-I Singleton\u2013Merten syndrome variant"],"prefix":"10.1093","volume":"33","author":[{"given":"Ahmed","family":"Abu Tayeh","sequence":"first","affiliation":[{"name":"Laboratory of Regulatory Information, Institute for Frontier Life and Medical Science, Kyoto University , Sakyo-ku, Kyoto,","place":["Japan"]},{"name":"Laboratory of Molecular and Cellular Immunology, Graduate School of Biostudies, Kyoto University , Sakyo-ku, Kyoto,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahide","family":"Funabiki","sequence":"additional","affiliation":[{"name":"Laboratory of Regulatory Information, Institute for Frontier Life and Medical Science, Kyoto University , Sakyo-ku, Kyoto,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shota","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Laboratory of Regulatory Information, Institute for Frontier Life and Medical Science, Kyoto University , Sakyo-ku, Kyoto,","place":["Japan"]},{"name":"Laboratory of Molecular and Cellular Immunology, Graduate School of Biostudies, Kyoto University , Sakyo-ku, Kyoto,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saya","family":"Satoh","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Immunology, University Hospital Bonn, University of Bonn , Bonn,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee","family":"Sumin","sequence":"additional","affiliation":[{"name":"Laboratory of Regulatory Information, Institute for Frontier Life and Medical Science, Kyoto University , Sakyo-ku, Kyoto,","place":["Japan"]},{"name":"Laboratory of Molecular and Cellular Immunology, Graduate School of Biostudies, Kyoto University , Sakyo-ku, Kyoto,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoichiro","family":"Iwakura","sequence":"additional","affiliation":[{"name":"Center for Animal Disease Models, Research Institute for Science and Technology, Tokyo University of Science , Yamazaki, Chiba,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Kato","sequence":"additional","affiliation":[{"name":"Laboratory of Regulatory Information, Institute for Frontier Life and Medical Science, Kyoto University , Sakyo-ku, Kyoto,","place":["Japan"]},{"name":"Institute of Cardiovascular Immunology, University Hospital Bonn, University of Bonn , Bonn,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Fujita","sequence":"additional","affiliation":[{"name":"Laboratory of Regulatory Information, Institute for Frontier Life and Medical Science, Kyoto University , Sakyo-ku, Kyoto,","place":["Japan"]},{"name":"Laboratory of Molecular and Cellular Immunology, Graduate School of Biostudies, Kyoto University , Sakyo-ku, Kyoto,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,10,29]]},"reference":[{"key":"2026041420062389000_CIT0001","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.mib.2014.05.011","article-title":"Sensing viral invasion by RIG-I like receptors","volume":"20","author":"Yoo","year":"2014","journal-title":"Curr. 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