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

点击翻译按钮获取中文摘要

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.