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In this study, we examined whether IgE-mediated systemic anaphylaxis was controlled by in vivo administration of IL-21 using the peanut allergy model in mice and investigated the molecular mechanisms underlying the IL-21-induced regulation of IgE. The anaphylactic reaction was completely abolished by the administration of recombinant mouse IL-21 or an IL-21 expression plasmid in terms of the change of body temperature and anaphylactic symptoms. The recombinant mouse IL-21 treatment remarkably suppressed IgE CSR in splenic B cells, resulting in significant decrease in serum concentrations of total as well as allergen-specific IgE. In the meanwhile, IL-21 provoked B cells in normal as well as allergic mice to express the inhibitor of differentiation 2 (Id2) gene that was shown to be crucially involved in the regulation of the activation-induced cytidine deaminase and IgE CSR. Moreover, mice genetically deficient for Id2 were completely unsusceptible to IL-21-induced prevention of IgE CSR and anaphylaxis. The present study strongly suggests that IL-21 is capable of regulating systemic allergic reactions by inducing the transcriptional regulator Id2, and the cytokine may be useful for clinical intervention for allergic diseases including anaphylaxis.<\/jats:p>","DOI":"10.4049\/jimmunol.179.12.8554","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:25:48Z","timestamp":1397849148000},"page":"8554-8561","source":"Crossref","is-referenced-by-count":43,"title":["IL-21 Induces Inhibitor of Differentiation 2 and Leads to Complete Abrogation of Anaphylaxis in Mice"],"prefix":"10.1093","volume":"179","author":[{"given":"Tsunao","family":"Kishida","sequence":"first","affiliation":[{"name":"Department of Microbiology, Kyoto Prefectural University of Medicine , Kamikyo, Kyoto ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yayoi","family":"Hiromura","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Kyoto Prefectural University of Medicine , Kamikyo, Kyoto ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaharu","family":"Shin-Ya","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Kyoto Prefectural University of Medicine , Kamikyo, Kyoto ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidetsugu","family":"Asada","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Kyoto Prefectural University of Medicine , Kamikyo, Kyoto ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroko","family":"Kuriyama","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Kyoto Prefectural University of Medicine , Kamikyo, Kyoto ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manabu","family":"Sugai","sequence":"additional","affiliation":[{"name":"Center for Molecular Biology and Genetics, Kyoto University, Shogoin-Kawahara , Sakyo, Kyoto ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Center for Molecular Biology and Genetics, Kyoto University, Shogoin-Kawahara , Sakyo, Kyoto ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshifumi","family":"Yokota","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, School of Medicine, University of Fukui , Shimoaizuki, Matsuoka, Fukui ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takemitsu","family":"Hama","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Kyoto Prefectural University of Medicine , Kamikyo, Kyoto ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiro","family":"Imanishi","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Kyoto Prefectural University of Medicine , Kamikyo, Kyoto ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuo","family":"Hisa","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Kyoto Prefectural University of Medicine , Kamikyo, Kyoto ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osam","family":"Mazda","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Kyoto Prefectural University of Medicine , Kamikyo, Kyoto ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2007,12,15]]},"reference":[{"key":"2026012809260107100_R1","first-page":"1230","volume-title":"J. 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