Epicutaneous antigen exposure primes for experimental eosinophilic esophagitis in mice
Epicutaneous antigen exposure primes for experimental eosinophilic esophagitis in mice
复制标题
DOI：
10.1053/j.gastro.2005.06.027
复制
发表时间：
2005-09-01
期刊：
影响因子：
29.4
通讯作者：
Rothenberg, ME
中科院分区：
文献类型：
--
作者：
Akei, HS;Mishra, A;Rothenberg, ME
背景与目的：嗜酸粒细胞性食管炎（EE）常与特应性疾病相关，包括皮炎和哮喘。有数据显示特应性皮肤可能为抗原致敏提供一个早期切入点。我们旨在验证经皮接触抗原是否会引发后续呼吸道抗原诱导的EE这一假说。方法：野生型和基因工程小鼠接受经皮抗原致敏以及实验性EE的诱导，并对免疫反应进行检测。结果：我们发现，通过经皮途径接触抗原会使食管在单次气道抗原激发后出现显著的嗜酸粒细胞性炎症。以卵清蛋白或烟曲霉作为经皮抗原时，实验性EE的发生与皮肤嗜酸粒细胞显著增多、骨髓嗜酸粒细胞生成加速、血液嗜酸粒细胞增多以及血清中抗原特异性免疫球蛋白G1/免疫球蛋白E大幅增加有关。对基因靶向小鼠的机制分析表明，白细胞介素 - 5是食管嗜酸粒细胞增多所必需的，白细胞介素 - 4、白细胞介素 - 13和STAT6的作用较小。结论：这些发现首次证明经皮接触过敏原可通过一种依赖Th2的机制强效引发EE。
Background & Aims: Eosinophilic esophagitis (EE) is frequently associated with atopic disease, including dermatitis and asthma. Data are emerging that atopic skin may provide an early entry point for antigen sensitization. We aimed to test the hypothesis that epicutaneous exposure to antigen primes for subsequent respiratory antigen-induced EE. Methods: Wild-type and genetically engineered mice were subjected to epicutaneous antigen sensitization and the development of experimental EE, and immune responses were examined. Results: We show that exposure to antigen via the epicutaneous route primes for marked eosinophilic inflammation in the esophagus triggered by a single airway antigen challenge. The development of experimental EE is associated with significant skin eosinophilia, accelerated bone marrow eosinophilopoiesis, blood eosinophilia, and large increases in serum antigen-specific immunoglobulin G1/immunoglobulin E using ovalbumin or Aspergillus fumigatus as the epicutaneous antigen. Mechanistic analysis with gene-targeted mice showed that interleukin-5 was required for esophageal eosinophilia and that interleukin-4, interleukin-13, and STAT6 contributed to a lesser extent. Conclusions: These findings provide the first evidence that epicutaneous exposure to allergens potently primes for EE via a Th2-dependent mechanism.