The impact of dietary proteins for mucosal homeostasis and inflammation

根据我们的初步发现，我们假设饮食蛋白质对维持正常的肠道免疫隔间和屏障功能是必不可少的。在这里，我们旨在揭示饮食蛋白质对健康和炎症肠道的肠道屏障功能和T细胞激活的影响。这将分三个步骤加以解决。A)通过对食物蛋白质的特定免疫识别实现肠道内环境稳定。我们将研究对肠道炎症的易感性是否与适应性免疫系统识别食物蛋白质有关。免疫活性、Rag1 KO和IL-10-Foxp3报告小鼠将被喂养常规(Conv)或无蛋白(Faf)饮食，以分析免疫反应、结肠炎发展和肠道屏障功能。B)饮食蛋白通过改变微生物群和基因表达来影响膜的完整性。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菌群的情况下给予蛋白质。这些实验将提供关于饮食改变微生物群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CD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。患者和对照组的肠道T细胞将在营养治疗(元素饮食或非肠道饮食)前后进行分析。此外，还将比较不同患者外周血中T细胞的激活情况。这些数据将提供深入的见解，饮食蛋白质如何调节粘膜和外周T细胞的激活，影响肠道屏障功能。

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.