Establishing the immuno-modulatory properties of dietary lipids on T cell function.

许多不同的生物拥有一种免疫系统，从基本的细菌对噬菌体感染的反应到脊椎动物的复杂和分层防御。组织炎症是哺乳动物对感染的免疫反应的关键部分，提供了有利于宿主免疫细胞(如T细胞)暂时集中和损伤/感染物质从该区域流出的局部条件。然而，有证据表明，尽管有更多的组织炎症，高脂肪饮食会导致免疫功能降低(影响T细胞功能)。然而，导致T细胞功能降低的机制仍然知之甚少。肠道是第一个与食物接触的器官。驻留在肠道中的免疫细胞可能在调节全身免疫功能方面发挥重要作用。饮食中的脂肪酸可以不同地调节炎症和免疫功能。例如，饱和脂肪酸似乎降低了免疫功能，而长链多不饱和脂肪酸则有相反的效果。特定的磷脂，如磷脂酰胆碱(PC)，也被证明可以增强哺乳期啮齿动物的肠道相关免疫功能。此外，给哺乳期啮齿类动物喂食PC可增强其后代的T细胞功能。总之，这表明PC在不同的生理条件下可能是T细胞功能的重要调节器。我的NSERC计划的目标是了解饮食脂质调节T细胞功能的机制。我的发现基金的短期到中期目标是了解导致Wistar大鼠T细胞功能降低(挑战后增殖减少)的潜在机制，以应对高脂肪饮食。特别是，我的计划将专注于了解饮食和肠道相关免疫系统之间的相互作用，以及它如何影响系统免疫功能。我这个项目的中长期目标是了解PC如何使T细胞功能正常化。我的总体工作假设是，高脂肪喂养会降低T细胞功能，但可以通过特定的饮食脂质，特别是PC来纠正。以下具体目标将得到解决：*1-研究饮食脂质调节Wistar大鼠T细胞功能的机制(直接和间接)。*2-了解饮食供应PC如何调节T细胞功能。*我的NSERC计划将有助于我们对饮食脂质和T细胞功能之间的生物学联系的基本理解，并将提供机制证据支持外源性PC供应以调节T细胞功能的建议。该计划将使用多学科方法结合不同的技术，受训人员将在动物模型、实验饮食、脂类代谢、生物化学和免疫学方面积累经验。

Many diverse organisms possess an immune system, from the rudimentary bacterial response to phage infection to the complex and layered defenses found in vertebrates. Tissue inflammation is a key part of the mammalian immune response to infection, providing localized conditions that are conducive to both a temporary concentration of host immune cells (e.g., T cells) and to the outflow of injured/infected material from the area. However, evidence has shown that a high-fat diet can result in lower immune function (affecting T cell function) despite having more tissue inflammation. Yet, the mechanisms responsible for this lower T cell function are still poorly understood. The gut is the first organ in contact with the foods. Immune cells that reside in the gut could play an important role in modulating immune function in the whole body. Dietary fatty acids can modulate inflammation and immune function differently. For instance, saturated fatty acids seem to lower immune function whereas long-chain polyunsaturated fatty acids have the opposite effect. Specific phospholipids such as phosphatidylcholine (PC) have also been shown to enhance the gut-associated immune function in lactating rodents. Moreover, feeding PC to lactating rodents enhanced T cell function in their offspring. Altogether this suggests that PC could be an important regulator of T cell function in different physiological conditions.******The goal of my NSERC program is to understand the mechanisms by which dietary lipids modulate T cell function. The short- to mid-term goal of my discovery grant is to understand the underlying mechanisms responsible for lower T cell function (reduced proliferation after challenge) in Wistar rats in response to a high-fat diet. In particular, my program will focus at understanding the interaction between diet and the gut-associated immune system and how it influences systemic immune function. The mid- to long-term goal of my program is to understand how PC can normalize T cell function. My overall working hypothesis is that high-fat feeding reduces T cell function but can be corrected by specific dietary lipids, particularly PC. The following specific objectives will be addressed: ******1- To investigate the mechanisms (direct and indirect) by which dietary lipids modulate T cell function in Wistar rats.***2- To understand how a dietary supply of PC modulates T cell function.******My NSERC program will contribute to our fundamental understanding of the biological connections between dietary lipids and T cell function and will provide the mechanistic evidence to support the recommendation of an exogenous supply of PC to regulate T cell function. This program will use a multidisciplinary approach combining different techniques and trainees will become experienced in animal models, experimental diets, lipids metabolism, biochemistry and immunology.