Abstract：
We have previously shown the ability of transamidated gluten (spf) to modulate both innate and adaptive intestinal immunity elicited by wheat gliadin in HLA-DQ8 transgenic mice (DQ8 mice), a model of gluten sensitivity. Herein, we evaluated the influence of spf when administered intragastrically on the immune response to native gliadin in DQ8 mice. To address the issue, we analysed three regimens of antigen administration: before immunisation (pre-treatment), during immunisation (co-treatment) and through breast milk during the lactating phase (suckling treatment). Mice were immunised mucosally by intranasal delivery of digested wheat gliadin along with cholera toxin in multiple doses. After sacrifice, isolated spleen and mesenteric lymph node (MLN) cells were challenged in vitro and the cytokine profile of culture supernatants assessed by ELISA and multiparametric assay. We found that only pre-treatment with spf was effective in down-regulating the gliadin-specific IFN-γ response and only in spleen cells. Interestingly, spf pre-treatment also induced systemic IL-6, IL-17A and TNF-α. By contrast, we found that spf pre-treatment upregulated INF-γ in MLN but also significantly decreased IL-2. In conclusion, our data provide evidence that the preventive intragastric administration of transamidated gluten is able to interfere with the classical cytokine profile induced by gliadin via mucosal immunisation in a transgenic model expressing one of the HLA molecules associated with coeliac disease.
摘要：
我们先前已经显示了转酰胺化谷蛋白（spf）在HLA-DQ8转基因小鼠（DQ8小鼠）中调节小麦麦醇溶蛋白引起的先天性和适应性肠道免疫的能力，面筋敏感性模型.在这里，我们评估了胃内给药spf对DQ8小鼠天然麦醇溶蛋白免疫应答的影响.为了解决这个问题，我们分析了三种抗原给药方案：免疫前（治疗前），在免疫期间（共同治疗）和在泌乳阶段通过母乳（哺乳治疗）。通过鼻内递送消化的小麦麦醇溶蛋白和多剂量的霍乱毒素对小鼠进行粘膜免疫。牺牲之后,在体外攻击分离的脾和肠系膜淋巴结（MLN）细胞，并通过ELISA和多参数测定评估培养上清液的细胞因子谱。我们发现，只有用spf预处理才能有效下调麦醇溶蛋白特异性IFN-γ反应，并且仅在脾细胞中有效。有趣的是,spf预处理还诱导全身性IL-6、IL-17A和TNF-α。相比之下,我们发现spf预处理上调MLN中的INF-γ，但也显着降低IL-2。总之,我们的数据提供了证据,表明在表达与乳糜泻相关的HLA分子之一的转基因模型中,预防性胃内施用转酰胺化谷蛋白能够通过粘膜免疫干扰麦醇溶蛋白诱导的经典细胞因子谱.
