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In the present study, we show that ablation of IL\u20104R\u03b1\u2013induced phosphatidylinositol 3\u2010kinase (PI3K) activating signal by germline point mutation within the IL\u20104R\u03b1 motif (Y500F) did not alter susceptibility to IgE\u2010mediated, food\u2010induced experimental anaphylaxis. Moreover, diarrhea occurrence, antigen\u2010specific IgE and intestinal mastocytosis were comparable between WT and IL\u20104R\u03b1<jats:sup>Y500F<\/jats:sup>mice. However, mice unable to stimulate IL\u20104R\u03b1\u2013mediated PI3K signaling had accelerated disease progression. Notably, the accelerated anaphylactic response was associated with more rapid histamine\u2010induced hypovolemia. Mechanistic in vitro and in vivo analyses revealed that endothelial IL\u20104R\u03b1 PI3K signaling negatively regulates the histamine\u2010induced endothelial leak response. These results define an unanticipated role for IL\u20104R\u03b1\u2013mediated PI3K signaling in negative regulation of IgE\u2010mediated anaphylactic reactions.<\/jats:p><\/jats:sec>","DOI":"10.1002\/iid3.80","type":"journal-article","created":{"date-parts":[[2015,9,17]],"date-time":"2015-09-17T06:56:42Z","timestamp":1442473002000},"page":"420-430","source":"Crossref","is-referenced-by-count":8,"title":["Loss of IL\u20104R\u03b1\u2013mediated PI3K signaling accelerates the progression of IgE\/mast cell\u2013mediated reactions"],"prefix":"10.1002","volume":"3","author":[{"given":"Jane","family":"Sledd","sequence":"first","affiliation":[{"name":"Divisions of Allergy and Immunology and of Immunobiology Department of Pediatrics University of Cincinnati College of Medicine Cincinnati Children's Hospital Medical Center 3333 Burnet Avenue Cincinnati OH 45229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Wu","sequence":"additional","affiliation":[{"name":"Divisions of Allergy and Immunology and of Immunobiology Department of Pediatrics University of Cincinnati College of Medicine Cincinnati Children's Hospital Medical Center 3333 Burnet Avenue Cincinnati OH 45229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Ahrens","sequence":"additional","affiliation":[{"name":"Divisions of Allergy and Immunology and of Immunobiology Department of Pediatrics University of Cincinnati College of Medicine Cincinnati Children's Hospital Medical Center 3333 Burnet Avenue Cincinnati OH 45229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeebong","family":"Lee","sequence":"additional","affiliation":[{"name":"Divisions of Allergy and Immunology and of Immunobiology Department of Pediatrics University of Cincinnati College of Medicine Cincinnati Children's Hospital Medical Center 3333 Burnet Avenue Cincinnati OH 45229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Waggoner","sequence":"additional","affiliation":[{"name":"Divisions of Allergy and Immunology and of Immunobiology Department of Pediatrics University of Cincinnati College of Medicine Cincinnati Children's Hospital Medical Center 3333 Burnet Avenue Cincinnati OH 45229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying Ting","family":"Tsai","sequence":"additional","affiliation":[{"name":"Divisions of Allergy and Immunology and of Immunobiology Department of Pediatrics University of Cincinnati College of Medicine Cincinnati Children's Hospital Medical Center 3333 Burnet Avenue Cincinnati OH 45229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yui\u2010Hsi","family":"Wang","sequence":"additional","affiliation":[{"name":"Divisions of Allergy and Immunology and of Immunobiology Department of Pediatrics University of Cincinnati College of Medicine Cincinnati Children's Hospital Medical Center 3333 Burnet Avenue Cincinnati OH 45229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon P.","family":"Hogan","sequence":"additional","affiliation":[{"name":"Divisions of Allergy and Immunology and of Immunobiology Department of Pediatrics University of Cincinnati College of Medicine Cincinnati Children's Hospital Medical Center 3333 Burnet Avenue Cincinnati OH 45229"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,9,17]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1081-1206(10)62363-0"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2009-1210"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2004.03.014"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2010.11.044"},{"key":"e_1_2_7_6_1","first-page":"1","article-title":"Food allergy among U.S. children: trends in prevalence and hospitalizations","author":"Branum A. 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