The impact of dietary proteins for mucosal homeostasis and inflammation

基于我们的初步发现，我们假设膳食蛋白质对于维持正常的肠道免疫区和屏障功能是必不可少的。在这里，我们的目的是揭示饮食蛋白质对健康和炎症肠道中肠道屏障功能和T细胞活化的影响。这个问题将分三步解决。A)肠道内稳态通过对食物蛋白质的特异性免疫识别。我们将研究肠道炎症的易感性是否与适应性免疫系统对食物蛋白质的识别有关。将免疫活性小鼠、Rag1 KO和IL-10-Foxp3报告小鼠分别饲喂常规（Conv）或无蛋白（FAF）饲料，分析其免疫应答、结肠炎发展和肠道屏障功能。B)膳食蛋白质通过改变微生物组和基因表达影响膜完整性。我们将剖析这两种成分对结肠炎发展和肠膜完整性的影响。实验方法包括粪便移植和/或在存在或不存在微生物群的情况下给药蛋白质。这些实验将提供关于饮食改变的微生物组和肠道基因表达变化对结肠炎易感性增加的影响的重要信息。C)克罗恩病（CD）患者的营养治疗。为了将小鼠的发现转化为人类疾病，我们将研究在乳糜泻患者中观察到的T细胞过度激活是否可以通过营养治疗来控制。将分析患者和对照组的肠道T细胞在营养治疗（元素或肠外饮食）前后的情况。此外，将比较患者外周血中的T细胞活化情况。这些数据将提供膳食蛋白质如何调节影响肠屏障功能的粘膜和外周T细胞活化的见解。

Based on our preliminary findings, we hypothesize that dietary proteins are essential for the maintenance of a normal intestinal immune compartment and barrier function. Here, we aim to reveal the effects of dietary protein on intestinal barrier function and T cell activation in the healthy and inflamed gut. This will be addressed in three steps. A) Intestinal homeostasis by specific immune recognition of food proteins. We will study whether susceptibility to intestinal inflammation is linked with recognition of food protein by the adaptive immune system. Immunocompetent, Rag1 KO and IL-10-Foxp3 reporter mice fed conventional (Conv) or protein-free (FAF) diet will be analysed for immunological responses, colitis development and intestinal barrier function. B) Dietary protein affects membrane integrity via an altered microbiome and gene expression. We will dissect the impact of both components on colitis development and intestinal membrane integrity. The experimental approach includes faecal transplantation and/or administration of protein in the presence or absence of microflora. These experiments will provide important information about the effects of a diet-altered microbiome and changes in intestinal gene expression for increased susceptibility to colitis. C) Nutritional therapies in Crohns disease (CD) patients. To translate the murine findings to human disease, we will study whether T cell hyperactivation observed in CD patients can be controlled by nutrional therapy. Intestinal T cells from patients and controls will be analyzed before and after nutritional therapy (elemental or parenteral diet). Further, T cell activation in the peripheral blood will be compared between patients. The data will provide insight how dietary protein regulates mucosal and peripheral T cell activation influencing the intestinal barrier function.