Wheat sensitivity: Impact of wheat varieties and wheat growing conditions on innate immunity

小麦敏感性：小麦品种和小麦生长条件对先天免疫的影响

• 批准号: 286494360
• 负责人: Professor Dr. Friedrich Longin
• 金额: --
• 依托单位: Landessaatzuchtanstalt (720)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2019-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/286494360?language=en
• 关键词: Wheat; sensitivity; Impact; wheat; varieties

Non-celiac wheat sensitivity (NCWS) is defined as an immunological reaction to ingestion of wheat that is not caused by celiac disease or wheat allergy. NCWS affects between 2% and 10% of wheat consuming subjects and is caused by an innate immune response to wheat proteins. Recently, we identified the family of wheat amylase-trypsin inhibitors (ATIs) as triggers of innate immunity. Wheat ATIs activate the toll like receptor 4 (TLR4)-MD2-CD14 complex, lead to the release of proinflammatory cytokines in dendritic cells>macrophages>monocytes and to the maturation of dendritic cells. Relevant TLR4 stimulating activity is confined to ATIs of gluten containing grains like wheat, rye and barley. Notably, we demonstrated that nutritional ATIs exacerbate experimental autoimmune and allergic diseases in a dose-dependent manner. Therefore, determination of ATI content, ATI bioactivity and of ATI-gene regulation in currently used and alternative wheat variants should be of high relevance to human health. To date, only a single wheat variety had been subjected to extensive transcriptome and proteome analysis, showing that ATIs represented 2-4% and gluten proteins >80% of total protein. Moreover, 19 DNA regions encoded potential ATIs. Since the expression of wheat genes and proteins is highly dependent on the wheat variety and growing conditions, studies with larger numbers of wheat varieties grown under different conditions are urgently needed, to better understand the regulation of ATI expression. This should allow the production of healthier wheat products, preventing enhanced morbidity due to wheat sensitivity and worsening of chronic inflammatory diseases.Our proposal combines the expertise of biomedicine, of wheat breeding and wheat growing research, and of genetics and proteomics, to study the role and the regulation of wheat ATIs and their in vitro and in vivo effects on innate and adaptive immunity. 160 wheat varieties comprising modern elite strains and important old varieties will be grown at 3 different field locations in Germany. The harvested samples will be subjected to examination of quality traits regularly selected by wheat breeders, advanced proteomic and genetic analyses focused on ATI expression, and to cell based in vitro TLR4 stimulatory activity. Select samples will be employed for in vivo feeding studies, addressing food matrix effects on intestinal and general ATI-induced innate and adaptive immune activation. Combined with thorough statistical analyses, the data will enable us to characterize ATI expression and bioactivity in a wide variety of wheats, grown under different conditions, to select for variants and conditions with low ATI expression and bioactivity. This will likely promote the growing of less immunogenic and therefore healthier wheat strains.

非乳糜泻小麦敏感性（NCWS）定义为对非乳糜泻或小麦过敏引起的小麦摄入的免疫反应。NCWS影响2%至10%的小麦消费受试者，由对小麦蛋白的先天免疫反应引起。最近，我们确定了小麦淀粉酶-胰蛋白酶抑制剂（ATI）家族作为先天免疫的触发因子。小麦ATI激活Toll样受体4（TLR 4）-MD 2-CD 14复合物，导致树突状细胞>巨噬细胞>单核细胞中促炎细胞因子的释放以及树突状细胞的成熟。相关的TLR 4刺激活性限于含谷蛋白的谷物如小麦、黑麦和大麦的ATI。值得注意的是，我们证明了营养性ATI以剂量依赖性方式加剧实验性自身免疫性和过敏性疾病。因此，ATI含量，ATI生物活性和ATI基因调控目前使用的和替代小麦变种的测定应与人类健康高度相关。迄今为止，只有一个小麦品种进行了广泛的转录组和蛋白质组分析，表明ATI占总蛋白质的2-4%，面筋蛋白>80%。此外，19个DNA区域编码潜在的ATI。由于小麦基因和蛋白质的表达高度依赖于小麦品种和生长条件，因此迫切需要研究在不同条件下生长的大量小麦品种，以更好地了解ATI表达的调控。这将有助于生产更健康的小麦产品，防止由于小麦敏感性和慢性炎症性疾病的恶化而导致的发病率增加。我们的建议结合了生物医学，小麦育种和小麦种植研究，遗传学和蛋白质组学的专业知识，研究小麦ATI的作用和调节及其在体外和体内对先天性和适应性免疫的影响。160个小麦品种包括现代优良品系和重要的老品种将在德国的3个不同的田间地点种植。收获的样品将进行小麦育种者定期选择的质量性状检查，集中于ATI表达的先进蛋白质组学和遗传分析，以及基于细胞的体外TLR 4刺激活性。选择的样品将用于体内喂养研究，解决食物基质对肠道和全身ATI诱导的先天性和适应性免疫激活的影响。结合全面的统计分析，这些数据将使我们能够表征ATI在不同条件下生长的各种小麦中的表达和生物活性，以选择具有低ATI表达和生物活性的变体和条件。这可能会促进免疫原性较低，因此更健康的小麦品种的生长。