title: Peanut-induced intestinal allergy is mediated through a mast cell-IgE-FcepsilonRI-IL-13 pathway.
abstract: BACKGROUND
  Although implicated in the disease, the specific contributions of FcepsilonRI and IL-13 to the pathogenesis of peanut-induced intestinal allergy are not well defined.
  
  
  OBJECTIVE
  We sought to determine the contributions of FcepsilonRI, IL-13, and mast cells to the development of intestinal mucosal responses in a murine model of peanut-induced intestinal allergy.
  
  
  METHODS
  Sensitized wild-type (WT), FcepsilonRI-deficient (FcepsilonRI(-/-)), and mast cell-deficient (Kit(W-sh/W-sh)) mice received peanut orally every day for 1 week. Bone marrow-derived mast cells (BMMCs) from WT, FcepsilonRI(-/-), IL-4(-/-), IL-13(-/-), and IL-4/IL-13(-/-) mice were differentiated and transferred into WT, FcepsilonRI(-/-), and Kit(W-sh/W-sh) recipients. BMMCs from WT and UBI-GFP/BL6 mice were differentiated and transferred into WT and Kit(W-sh/W-sh) mice. Blockade of IL-13 was achieved by using IL-13 receptor alpha2 (IL-13Ralpha2)-IgG fusion protein.
  
  
  RESULTS
  FcepsilonRI(-/-) mice showed decreased intestinal inflammation (mast cell and eosinophil numbers) and goblet cell metaplasia and reduced levels of IL4, IL6, IL13, and IL17A mRNA expression in the jejunum. Transfer of WT BMMCs to FcepsilonRI(-/-) recipients restored their ability to develop intestinal allergic responses unlike transfer of FcepsilonRI(-/-), IL-13(-/-), or IL-4/IL-13(-/-) BMMCs. FcepsilonRI(-/-) mice exhibited lower IL-13 levels and treatment of WT mice with IL-13 receptor alpha2 prevented peanut-induced intestinal allergy and inflammation.
  
  
  CONCLUSIONS
  These data indicate that the development of peanut-induced intestinal allergy is mediated through a mast cell-dependent IgE-FcepsilonRI-IL-13 pathway. Targeting IL-13 might be a potential treatment for IgE-mediated peanut-induced allergic responses in the intestine.
authors.affiliation: Division of Cell Biology, Department of Pediatrics, National Jewish Health, Denver, Colo, USA.
authors.forename: Meiqin
authors.initials: M
authors.lastname: Wang
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Takeda
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Shiraishi
authors.forename: Masakazu
authors.initials: M
authors.lastname: Okamoto
authors.forename: Azzeddine
authors.initials: A
authors.lastname: Dakhama
authors.forename: Anthony
authors.initials: A
authors.lastname: Joetham
authors.forename: Erwin W
authors.initials: EW
authors.lastname: Gelfand
mesh_terms: D000818:Animals; D010367:Arachis / Q000009:adverse effects*; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D018928:Immunity, Mucosal / Q000235:genetics / Q000276:immunology; D007073:Immunoglobulin E / Q000235:genetics / Q000276:immunology*; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000494:pharmacology; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D018793:Interleukin-13 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D053663:Interleukin-13 Receptor alpha2 Subunit / Q000235:genetics; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D007422:Intestines / Q000276:immunology / Q000473:pathology; D008407:Mast Cells / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D021183:Peanut Hypersensitivity / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D017455:Receptors, IgE / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology
chemical_list: C098680:Il17a protein, mouse; D007141:Immunoglobulin Fc Fragments; D018793:Interleukin-13; D053663:Interleukin-13 Receptor alpha2 Subunit; D020381:Interleukin-17; D015850:Interleukin-6; D017455:Receptors, IgE; D011993:Recombinant Fusion Proteins; D015847:Interleukin-4; D007073:Immunoglobulin E