期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 126, 期 2, 页码 306-U43出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2010.05.017
关键词
Peanut; intestinal allergy; mast cell; IgE; Fc epsilon RI; IL-13
资金
- National Institutes of Health [HL-36577, HL-61005, AI-77609]
Background: Although implicated in the disease, the specific contributions of Fc epsilon RI and IL-13 to the pathogenesis of peanut-induced intestinal allergy are not well defined. Objectives: We sought to determine the contributions of FceRI, 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), Fc epsilon RI-deficient (Fc epsilon RI(-/-)), 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, Fc epsilon RI(-/-), IL-4(-/-), IL-13(-/-), and IL-4/IL-13(-/-) mice were differentiated and transferred into WT, Fc epsilon RI(-/-), 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 alpha 2 (IL-13R alpha 2)-IgG fusion protein. Results: Fc epsilon RI(-/-) 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 Fc epsilon RI(-/-) recipients restored their ability to develop intestinal allergic responses unlike transfer of Fc epsilon RI(-/-), IL-13(-/-), or IL-4/IL-13(-/-) BMMCs. Fc epsilon RI(-/-) mice exhibited lower IL-13 levels and treatment of WT mice with IL-13 receptor alpha 2 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-Fc epsilon RI-IL-13 pathway. Targeting IL-13 might be a potential treatment for IgE-mediated peanut-induced allergic responses in the intestine. (J Allergy Clin Immunol 2010;126:306-16.)
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