Modulation of T cell function and development through the manipulation of diet-derived long chain polyunsaturated fatty acids

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The overall goal of my NSERC program is to determine how polyunsaturated fatty acids (PUFA) in the diet affect immunity. T cells are key components of the immune system and their function changes over the lifecycle. An important function of these cells is establishing 'oral tolerance', which is the body's ability to distinguish between beneficial and harmful dietary proteins. The ability of T cells to function develops early in life and our previous work has demonstrated that the type of fat in the diet influences development. For the first part of our NSERC program, we would like to determine the best balance of PUFA in the diet to ensure optimal T cell function and immune development, by conducting a series of experiments using rodent models. It is thought that PUFA likely affect T cell function by changing in the composition and/or content of lipids in the cell membrane. Exactly how a change in plasma membrane fats alters T cell function has not been established and is the focus of the second part of my NSERC program. We will be studying specialized parts of the cell membrane called 'lipid rafts'. Lipid rafts are involved in generating signaling messages that direct the function of T cells. We propose to study how a change in the fat composition of the lipid raft affects the messages generated in the cell and how that ultimately directs how a cell functions. Our studies will provide a fundamental understanding of the role of fats in the diet on the essential functions of T cells early in life and will assist in defining fatty acid requirements to optimize the immune health of infants.