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首页> 外文期刊>Clinical and experimental allergy : >Allergen-specific antibody and cytokine responses, mast cell reactivity and intestinal permeability upon oral challenge of sensitized and tolerized mice.
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Allergen-specific antibody and cytokine responses, mast cell reactivity and intestinal permeability upon oral challenge of sensitized and tolerized mice.

机译：致敏和耐受小鼠口服攻击后，变应原特异性抗体和细胞因子反应，肥大细胞反应性和肠道通透性。

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BACKGROUND: Food allergy has reached an epidemic level in westernized countries and although central mechanisms have been described, the variability associated with genetic diversity underscores the still unresolved complexity of these disorders. OBJECTIVE: To develop models of food allergy and oral tolerance, both strictly induced by the intestinal route, and to compare antigen-specific responses. METHODS: BALB/c mice were mucosally sensitized to ovalbumin (OVA) in the presence of the mucosal adjuvant cholera toxin, or tolerized by intra-gastric administrations of OVA alone. Antibody titres and cytokines were determined by ELISA, and allergic status was determined through several physiologic parameters including decline in temperature, diarrhoea, mast cell degranulation and intestinal permeability. RESULTS: OVA-specific antibodies (IgE, IgGs and IgA in serum and feces) were produced in sensitized mice exclusively. Upon intra-gastric challenge with OVA, sensitized mice developed anaphylactic reactions associated with a decline of temperature, diarrhoea, degranulation of mast cells, which were only moderately recruited in the small intestine, and increased intestinal permeability. Cytokines produced by immune cells from sensitized mice included T-helper type 2 cytokines (IL-5, IL-13), but also IL-10, IFN-gamma and IL-17. In contrast, all markers of allergy were totally absent in tolerized animals, and yet the latter were protected from subsequent sensitization, demonstrating that oral tolerance took place efficiently. CONCLUSION: This work allows for the first time an appropriate comparison between sensitized and tolerized BALB/c mice towards OVA. It highlights important differences from other models of allergy, and thus questions some of the generally accepted notions of allergic reactions, such as the protective role of IFN-gamma, the importance of antigen-specific secretory IgA and the role of mucosal mast cells in intestinal anaphylaxis. In addition, it suggests that IL-17 might be an effector cytokine in food allergy. Finally, it demonstrates that intestinal permeability towards the allergen is increased during challenge.
机译：背景：在西方国家，食物过敏已达到流行水平，尽管已经描述了主要机制，但与遗传多样性相关的变异性强调了这些疾病的尚未解决的复杂性。目的：建立严格由肠途径诱导的食物过敏和口服耐受性模型，并比较抗原特异性反应。方法：在存在黏膜佐剂霍乱毒素的情况下，对BALB / c小鼠黏膜对卵清蛋白（OVA）致敏，或仅在腹腔内给予OVA耐受。通过ELISA确定抗体滴度和细胞因子，并通过几个生理参数确定过敏状态，包括温度下降，腹泻，肥大细胞脱粒和肠通透性。结果：OVA特异性抗体（血清和粪便中的IgE，IgG和IgA）仅在致敏小鼠中产生。在用OVA进行胃内攻击后，致敏的小鼠会产生与温度下降，腹泻，肥大细胞脱粒有关的过敏反应，这些反应仅在小肠中度募集，并增加了肠的通透性。致敏小鼠免疫细胞产生的细胞因子包括2型T辅助细胞因子（IL-5，IL-13），还包括IL-10，IFN-γ和IL-17。相比之下，在耐受的动物中完全没有过敏的所有标志物，但是对后者进行了保护，使其免受随后的致敏作用，这表明有效的口服耐受性。结论：这项工作首次使致敏和耐受的BALB / c小鼠对OVA有了适当的比较。它突显了与其他变态反应模型的重要区别，因此质疑了一些普遍公认的变态反应概念，例如IFN-γ的保护作用，抗原特异性分泌型IgA的重要性以及粘膜肥大细胞在肠道中的作用过敏反应。另外，它暗示IL-17可能是食物过敏中的效应细胞因子。最后，它表明挑战过程中肠道对过敏原的通透性增加。

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