Division of Cell Biology, Department of Pediatrics, National Jewish Health, Denver, Colo, USA.
J Allergy Clin Immunol. 2010 Aug;126(2):306-16, 316.e1-12. doi: 10.1016/j.jaci.2010.05.017. Epub 2010 Jul 10.
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.
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.
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.
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.
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.
虽然已经涉及到疾病，但 FcepsilonRI 和 IL-13 对花生诱导的肠道过敏发病机制的具体贡献尚不清楚。
我们试图确定 FcepsilonRI、IL-13 和肥大细胞在花生诱导的肠道过敏的小鼠模型中对肠道黏膜反应发展的贡献。
用花生对致敏的野生型（WT）、FcepsilonRI 缺陷（FcepsilonRI(-/-)）和肥大细胞缺陷（Kit(W-sh/W-sh)）小鼠进行每天口服 1 周的处理。从 WT、FcepsilonRI(-/-)、IL-4(-/-)、IL-13(-/-)和 IL-4/IL-13(-/-)小鼠分化骨髓来源的肥大细胞（BMMCs）并转移到 WT、FcepsilonRI(-/-)和 Kit(W-sh/W-sh)接受者中。从 WT 和 UBI-GFP/BL6 小鼠分化和转移 BMMCs 到 WT 和 Kit(W-sh/W-sh)小鼠中。通过使用 IL-13 受体 alpha2（IL-13Ralpha2）-IgG 融合蛋白来阻断 IL-13。
FcepsilonRI(-/-) 小鼠表现出减少的肠道炎症（肥大细胞和嗜酸性粒细胞数量）和杯状细胞化生以及空肠中 IL4、IL6、IL13 和 IL17A mRNA 表达水平降低。WT BMMCs 的转移恢复了 FcepsilonRI(-/-)接受者发展肠道过敏反应的能力，而转移 FcepsilonRI(-/-)、IL-13(-/-)或 IL-4/IL-13(-/-) BMMCs 则不行。FcepsilonRI(-/-) 小鼠表现出较低的 IL-13 水平，用 IL-13 受体 alpha2 治疗 WT 小鼠可预防花生诱导的肠道过敏和炎症。
这些数据表明，花生诱导的肠道过敏的发展是通过 IgE-FcepsilonRI-IL-13 途径介导的，通过靶向 IL-13 可能成为 IgE 介导的肠道中花生诱导的过敏反应的潜在治疗方法。
