DBV Technologies, Pépinière Santé Paris Cochin, Paris, France.
PLoS One. 2012;7(2):e31967. doi: 10.1371/journal.pone.0031967. Epub 2012 Feb 21.
Food allergy may affect the gastrointestinal tract and eosinophilia is often associated with allergic gastrointestinal disorders. Allergy to peanuts is a life-threatening condition and effective and safe treatments still need to be developed. The present study aimed to evaluate the effects of sustained oral exposure to peanuts on the esophageal and jejunal mucosa in sensitized mice. We also evaluated the effects of desensitization with epicutaneous immunotherapy (EPIT) on these processes.
Mice were sensitized by gavages with whole peanut protein extract (PPE) given with cholera toxin. Sensitized mice were subsequently exposed to peanuts via a specific regimen and were then analysed for eosinophilia in the esophagus and gut. We also assessed mRNA expression in the esophagus, antibody levels, and peripheral T-cell response. The effects of EPIT were tested when intercalated with sensitization and sustained oral peanut exposure.
Sustained oral exposure to peanuts in sensitized mice led to severe esophageal eosinophilia and intestinal villus sub-atrophia, i.e. significantly increased influx of eosinophils into the esophageal mucosa (136 eosinophils/mm(2)) and reduced villus/crypt ratios (1.6±0.15). In the sera, specific IgE levels significantly increased as did secretion of Th2 cytokines by peanut-reactivated splenocytes. EPIT of sensitized mice significantly reduced Th2 immunological response (IgE response and splenocyte secretion of Th2 cytokines) as well as esophageal eosinophilia (50 eosinophils/mm(2), p<0.05), mRNA expression of Th2 cytokines in tissue--eotaxin (p<0.05), IL-5 (p<0.05), and IL-13 (p<0.05)--GATA-3 (p<0.05), and intestinal villus sub-atrophia (2.3±0.15). EPIT also increased specific IgG2a (p<0.05) and mRNA expression of Foxp3 (p<0.05) in the esophageal mucosa.
Gastro-intestinal lesions induced by sustained oral exposure in sensitized mice are efficaciously treated by allergen specific EPIT.
食物过敏可能影响胃肠道，而嗜酸性粒细胞增多常与过敏性胃肠疾病有关。花生过敏是一种危及生命的情况，仍需要开发有效和安全的治疗方法。本研究旨在评估持续口服暴露于花生对致敏小鼠食管和空肠黏膜的影响。我们还评估了经皮免疫治疗（EPIT）脱敏对这些过程的影响。
通过给予霍乱毒素灌胃全花生蛋白提取物（PPE）使小鼠致敏。随后，致敏小鼠通过特定方案暴露于花生，并分析食管和肠道中的嗜酸性粒细胞增多。我们还评估了食管中的 mRNA 表达、抗体水平和外周 T 细胞反应。当与致敏和持续口服花生暴露相结合时，测试了 EPIT 的效果。
在致敏小鼠中持续口服暴露于花生会导致严重的食管嗜酸性粒细胞增多和小肠绒毛萎缩，即显著增加嗜酸性粒细胞进入食管黏膜的数量（136 个/平方毫米），并降低绒毛/隐窝比（1.6±0.15）。在血清中，特异性 IgE 水平显著增加，花生再激活的脾细胞分泌的 Th2 细胞因子也显著增加。致敏小鼠的 EPIT 显著降低了 Th2 免疫反应（IgE 反应和脾细胞分泌 Th2 细胞因子）以及食管嗜酸性粒细胞增多（50 个/平方毫米，p<0.05），组织中的 Th2 细胞因子 mRNA 表达——嗜酸性粒细胞趋化因子（p<0.05）、白细胞介素-5（p<0.05）和白细胞介素-13（p<0.05）——GATA-3（p<0.05），以及小肠绒毛萎缩（2.3±0.15）。EPIT 还增加了食管黏膜中的特异性 IgG2a（p<0.05）和 Foxp3 mRNA 表达（p<0.05）。
致敏小鼠经持续口服暴露引起的胃肠病变通过过敏原特异性 EPIT 得到有效治疗。
