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

在家禽饲养中减少抗菌剂的使用可以通过增强鸡的天然免疫力来实现，从而最大限度地减少疾病和病原体的脱落。干预卵内小鸡的免疫系统对孵化后的鸟的免疫力具有显著影响，增加其抵抗疾病挑战的能力。然而，不仅小鸡的免疫系统必须加强，成年鸟的免疫系统也必须加强。产蛋鸡的营养状况直接影响鸡蛋的营养成分，进而影响胚胎和孵化鸡的发育和营养状况。这对基因表达的表观遗传调控有影响，允许分裂细胞记忆或印记发生在其发育早期的信号事件。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，在种母鸡的饮食中加入叶酸会通过BCR和TCR基因甲基化状态影响B细胞前体发育，从而增强胚胎中B细胞的发育。在这项研究计划中，早期宿主先天性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）的表观遗传调节和细胞成熟时的细胞因子产生。该计划将进一步整合表观遗传表征，B细胞发育和免疫评估，并使用叶酸生产益生菌作为表观遗传修饰剂进行口服营养干预。本研究的主要目的是：（1）研究BCR细胞内信号蛋白IgG 1、MHC II、TLR-2和TLR-4基因在B细胞前体中的表观遗传学变化，并鉴定甲基化调控的基因;（2）确定甲基供体的包含是否与V（D）J重组中的DNA甲基化以及TLR-2和TLR-4基因的预测启动子区的DNA甲基化相关;（3）确定通过DNA甲基化的表观遗传编程是否调节基因表达。这项研究的结果不仅对家禽业有重要的实际应用，而且还将更好地了解DNA甲基化和去甲基化介导的染色质重塑如何通过BCR和TCR在调节V（D）J区域重组和生殖系转录中发挥重要作用。这些信息将提高我们对鸡胚胎B细胞发育和成熟的理解，并将开发整合营养干预和表观遗传免疫结果的模型。确定益生菌在促进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）。可能从营养干预战略中受益最大 **

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**