Peanut-induced intestinal allergy is mediated through a mast cell-IgE-Fc[epsilon]RI-IL-13 pathway

• Published in: Journal of allergy and clinical immunology Vol. 126; no. 2; p. 306
• Main Authors: Wang, Meiqin, Takeda, Katsuyuki, Shiraishi, Yoshiki, Okamoto, Masakazu, Dakhama, Azzeddine, Joetham, Anthony, Gelfand, Erwin W
• Format: Journal Article
• Language: English
• Published: St. Louis Elsevier Limited 01.08.2010
• Subjects: Allergies; Cytokines; Food allergies; Rodents
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2010.05.017

Background Although implicated in the disease, the specific contributions of FcεRI and IL-13 to the pathogenesis of peanut-induced intestinal allergy are not well defined. Objectives We sought to determine the contributions of FcεRI, 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), FcεRI-deficient (FcεRI-/-), and mast cell-deficient (KitW-sh/W-sh) mice received peanut orally every day for 1 week. Bone marrow-derived mast cells (BMMCs) from WT, FcεRI-/-, IL-4-/-, IL-13-/-, and IL-4/IL-13-/-mice were differentiated and transferred into WT, FcεRI-/-, and KitW-sh/W-shrecipients. BMMCs from WT and UBI-GFP/BL6 mice were differentiated and transferred into WT and KitW-sh/W-shmice. Blockade of IL-13 was achieved by using IL-13 receptor α2 (IL-13Rα2)-IgG fusion protein. Results FcεRI-/-mice showed decreased intestinal inflammation (mast cell and eosinophil numbers) and goblet cell metaplasia and reduced levels ofIL4, IL6, IL13, and IL17AmRNA expression in the jejunum. Transfer of WT BMMCs to FcεRI-/-recipients restored their ability to develop intestinal allergic responses unlike transfer of FcεRI-/-, IL-13-/-, or IL-4/IL-13-/-BMMCs. FcεRI-/-mice exhibited lower IL-13 levels and treatment of WT mice with IL-13 receptor α2 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-FcεRI-IL-13 pathway. Targeting IL-13 might be a potential treatment for IgE-mediated peanut-induced allergic responses in the intestine.