中文摘要
食物过敏影响着婴幼儿的生长发育,我国儿童食物过敏检出率为6.2%。国外研究表明食物过敏儿童粪钙卫蛋白水平增高,但具体分子机制研究尚属空白。我们前期研究发现过敏大鼠血及粪钙卫蛋白水平均显著高于非过敏大鼠,这提示钙卫蛋白存在、并有可能作用于食物过敏反应中。文献报道钙卫蛋白是TLR4的配体,食物过敏儿童中肠粘膜TLR4表达也显著增加。据此我们提出假说:钙卫蛋白可能通过TLR4作用活化DC及相关信号传导等,引起过敏及炎症相关的免疫反应。本课题将通过建立食物过敏大鼠模型检测钙卫蛋白、相关过敏及炎症因子等水平变化,再通过细胞水平研究钙卫蛋白对CD4+T细胞及树突状细胞活化的影响,首次探讨钙卫蛋白在食物过敏发生和发展中的作用及分子机制。首次通过队列研究,比较食物过敏和非过敏婴幼儿粪钙卫蛋白的变化及差异,评估其在婴幼儿食物过敏的预测及监测作用,以最终达到减少儿童食物过敏性疾病发生及引起的相关危害的目的。
英文摘要
Food allergy affects the growth and development of infants and children, the prevalence of food allergy in children in China was 6.2%. Foreign studies have shown that the level of fecal calprotectin in children with food allergy increased, but the specific molecular mechanism of calprotectin in food allergy is still blank. In our preliminary study, we found that the levels of calprotectin in both blood and feces of allergic rats were significantly higher than those in control rats, suggesting that calprotectin may exist and play an important role in food allergy. Published literature reported that calprotectin was an activator of Toll-like receptor 4. Besides, the TLR4 expression also increased significantly in the intestines of children with food allergy. Therefore, we speculated that the calprotectin may activate DC and related signal transduction by TLR4, which may induce allergic and inflammatory related immune responses. On the basis of those results and speculation, the present proposal will establish immature rats model of food allergy and S100A9 knockout rat model to detect the expression levels of allergic and inflammatory factors such as calprotectin, toll-like receptor 4, nuclear factor kappa B, tumor necrosis factor-α, interleukin-6, interleukin-8, interferon-γ, interleukin-4, interleukin-5, interleukin-13 and ovalbumin-IgE in different organizations. Furthermore, the impact of calprotectin on CD4+ T cells and dendritic cell activation at the cellular level and the role of calprotectin in allergy activation will be explored. It is the first time that our study is to explore and determine the role and related molecular mechanism of calprotectin in the occurrence and development of food allergy. Simultaneously, the changes and differences of fecal calprotectin between food allergic and non-allergic infants will be observed and compared through our cohort study for the first time. Moreover, whether calprotectin as a noninvasive and sensitive biological marker could be contributed to the prediction and monitoring of food allergy in infants and young children will be evaluated, in order to reach the purpose of reducing the occurrence and harm of allergic disease in children eventually.
