我们已发表文章表明炎症细胞因子抑制CD4+ T细胞分泌IL-2，并分化为表达IL－4 的非经典Th2细胞而增加婴幼儿IgE介导的食物过敏的发病风险（Sci Transl Med, 2016）。体外预实验进一步证明，在CD8+ T细胞中，炎症因子促进脂肪酸代谢，并通过激活caspase而生成IL-4。我们假设炎症环境通过改变肠道T细胞的表观遗传和代谢途径，促进肠道T细胞的脂肪酸代谢和caspase－依赖的Th2/Tc2分化而介导肠道黏膜病变。我们将比较过敏和非过敏儿童结肠黏膜和外周血T细胞亚群的表型和功能，阐述T细胞亚群的表观遗传和转录组学特征，并利用过敏儿童结肠黏膜和食物过敏动物模型来验证肠道炎症诱发食物过敏的脂肪酸代谢和caspase活化调控机制。这将增加对食物过敏肠道局部免疫致病机制的了解，为疾病的诊断和治疗提供新的分子标签和药物靶点。

Previously we found that inflammatory cytokines suppressed IL-2 expression in CD4+T cells and promoted non-classical Th2 cell differentiation and the development of IgE-mediated food allergy in infants （Sci Transl Med, 2016）. In CD8+ T cells, preliminary data reveal that inflammation promoted fatty acid metabolism and caspase-dependent IL-4 expression. We hypothesize that inflammation and microbial metabolites alter the epigenetic and metabolic state of gastrointestinal resident T cells and mediate mucosal pathology through activation of fatty acid metabolism and caspase-dependent IL-4 expression. We will compare the phenotype and function of blood and gastrointestinal resident T cells in children with and without food allergy, and identify underlying mechanisms through integration of epigenetic and transcriptional data sets. We will confirm fatty acid metabolism and caspase-dependent Th2/Tc2 differentiation pathway in colon mucosa of children with food allergy and in animal models of food-allergy. This will broaden our understanding on the immunopathogenic mechanisms underlie childhood food allergy, and identify potential biomarkers and targets for disease diagnosis and therapy.