Nutritional regulation of genes associated with avian B cell receptors involved in innate and adaptive immunity

与先天性和适应性免疫相关的禽类 B 细胞受体相关基因的营养调节

• 批准号: RGPIN-2015-03839
• 负责人: RodriguezLecompte, Juan
• 金额: $ 1.75万
• 依托单位: University of Prince Edward Island
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=630565
• 关键词: Nutritional; regulation; genes; associated; avian

Reducing the use of antimicrobials in the rearing of poultry can be achieved by enhancing the natural immunity of chickens, thus minimizing disease and pathogen shedding. Intervention of the immune system of the chick in ovo has a dramatic effect on the immunity of the bird post-hatch, increasing its ability to resist a disease challenge. However, it is not only the chick’s immune system that must be strengthened but also that of the adult bird. The nutritional status of the laying hen directly influences the nutrient composition of the egg and, in turn, the development and nutritional status of the embryo and hatchling. This has implications for epigenetic regulation of gene expression allowing dividing cells to memorize, or imprint, signalling events that occurred earlier in their development. Folate plays a critical role in nucleic acid and protein synthesis; a deficiency of folate significantly alters the immune response. My hypothesis is that the inclusion of folate in breeder hens’ diet will enhance B cell development in the embryo by influencing B cell precursor development through BCR and TCR gene methylation status. In this research program, correlation between early host innate and adaptive immune system development and maturation will be used to explain epigenetic regulation at the antigen receptors (BCR and TLR) and cytokine production as the cells mature. This program will furthermore integrate epigenetic characterization, B cell development, and immunity evaluation with oral nutrition intervention using folate-producing probiotics as epigenetic modifiers. The main objectives of this research program are to: (1) Study epigenetic changes associated with BCR intracellular signalling protein Igß, MHC II, and TLR-2 and TLR-4 genes in B cell precursors, and identify genes under methylation regulation; (2) Determine whether inclusion of methyl donor is correlated with DNA methylation in V(D)J recombination and in the predicted promoter region of TLR-2 and TLR4 genes; (3) Determine whether epigenetic programming via DNA methylation regulates gene expression. The outcome of this research will not only have important practical application for the poultry industry, but will also yield a better understanding of how chromatin remodelling mediated by DNA methylation and demethylation plays a major role in regulating V(D)J regions recombination and germ line transcription through the BCR and TCR. The information will improve our understanding of B cell development and maturation in chicken embryos, and will develop models integrating nutritional intervention and epigenetic immune outcome. Determining the effect of probiotics in boosting the immune response is critical to the future of the Canadian Poultry Industry (nutrition and animal health) as it will help determine which breeding stage (laying hens, broilers, etc.) may benefit the most from nutritional intervention strategies

通过增强鸡的天然免疫力，可以减少家禽饲养中抗菌剂的使用，从而最大限度地减少疾病和病原体的脱落。干预雏鸟的免疫系统对雏鸟孵化后的免疫有显著的影响，增加其抵抗疾病挑战的能力。然而，不仅雏鸟的免疫系统需要加强，成年鸟的免疫系统也需要加强。蛋鸡的营养状况直接影响鸡蛋的营养成分，进而影响胚胎和幼雏的发育和营养状况。这暗示了基因表达的表观遗传调控，允许分裂细胞记忆或印记，在其发育早期发生的信号事件。叶酸在核酸和蛋白质合成中起着关键作用；叶酸缺乏会显著改变免疫反应。我的假设是，在种鸡饲粮中添加叶酸会通过BCR和TCR基因甲基化状态影响B细胞前体发育，从而促进胚胎中B细胞的发育。在本研究计划中，早期宿主先天和适应性免疫系统发育和成熟之间的相关性将用于解释抗原受体（BCR和TLR）和细胞因子在细胞成熟过程中的表观遗传调控。该项目将进一步整合表观遗传特征、B细胞发育和免疫评估，并使用叶酸生成益生菌作为表观遗传修饰剂进行口服营养干预。本课题的主要目标是：(1)研究B细胞前体中BCR细胞内信号蛋白Igß、MHC II、TLR-2和TLR-4基因的表观遗传变化，并鉴定受甲基化调控的基因；(2)确定在V(D)J重组和TLR-2和TLR4基因的预测启动子区域中，甲基供体的包含是否与DNA甲基化相关；(3)通过DNA甲基化确定表观遗传编程是否调控基因表达。该研究结果不仅对家禽业具有重要的实际应用价值，而且有助于更好地了解DNA甲基化和去甲基化介导的染色质重塑如何通过BCR和TCR调控V(D)J区重组和种系转录。这些信息将提高我们对鸡胚胎中B细胞发育和成熟的理解，并将开发综合营养干预和表观遗传免疫结果的模型。确定益生菌在增强免疫反应方面的作用对加拿大家禽业（营养和动物健康）的未来至关重要，因为它将有助于确定哪个繁殖阶段（蛋鸡、肉鸡等）可能从营养干预策略中获益最多