Allergen-specific antibody and cytokine responses, mast cell reactivity and intestinal permeability upon oral challenge of sensitized and tolerized mice
Allergen-specific antibody and cytokine responses, mast cell reactivity and intestinal permeability upon oral challenge of sensitized and tolerized mice
复制标题
DOI：
10.1111/j.1365-2222.2009.03329.x
复制
发表时间：
2010-01-01
影响因子：
6.1
通讯作者：
Corthesy, B.
中科院分区：
文献类型：
--
作者：
Perrier, C.;Thierry, A. -C.;Corthesy, B.
背景食物过敏在西方国家已经达到流行病的程度，尽管已经描述了中心机制，但与遗传多样性相关的变异性强调了这些疾病仍然未解决的复杂性。和比较抗原特异性respons.MethodsBALB/c小鼠粘膜致敏卵清蛋白（OVA）的存在下，粘膜佐剂霍乱毒素，或耐受胃内给药的OVA单独。抗体滴度和细胞因子的ELISA测定，过敏状态确定通过几个生理参数，包括温度下降，腹泻，肥大细胞脱粒和肠permeability. ResultsOVA特异性抗体（IgE，IgG和伊加在血清和粪便中）在致敏小鼠专门。在用OVA进行胃内激发后，致敏小鼠发生了与体温下降、腹泻、肥大细胞脱粒（其仅在小肠中中度募集）和肠通透性增加相关的过敏反应。由来自致敏小鼠的免疫细胞产生的细胞因子包括T辅助细胞2型细胞因子（IL-5、IL-13），但也包括IL-10、IFN-γ和IL-17。与此相反，所有的过敏标志物是完全不存在的耐受的动物，但后者受到保护，从随后的致敏，表明口服耐受发生efficient.ConclusionThis工作允许第一次致敏和耐受的BALB/c小鼠对OVA之间的适当比较。它突出了与其他过敏模型的重要差异，因此质疑了一些普遍接受的过敏反应概念，如IFN-γ的保护作用，抗原特异性分泌型伊加的重要性和粘膜肥大细胞在肠道过敏反应中的作用。提示IL-17可能是食物过敏的效应细胞因子。最后，它证明了肠道对过敏原的渗透性在攻击过程中增加。Perrier，A. C. Thierry，A.雇佣兵和B。Corthesy，临床与实验过敏，2010（40）153-162。
P>BackgroundFood 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.ObjectiveTo develop models of food allergy and oral tolerance, both strictly induced by the intestinal route, and to compare antigen-specific responses.MethodsBALB/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.ResultsOVA-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.ConclusionThis 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.Cite this as: C. Perrier, A.-C. Thierry, A. Mercenier and B. Corthesy, Clinical & Experimental Allergy, 2010 (40) 153-162.