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

我的NSERC计划的总体目标是确定饮食中的多不饱和脂肪酸（PUFA）如何影响免疫力。 T细胞是免疫系统的关键组成部分，其功能在生命周期中发生变化。 这些细胞的一个重要功能是建立“口服耐受性”，这是身体区分有益和有害膳食蛋白质的能力。 T细胞的功能在生命早期发展，我们以前的工作已经证明饮食中的脂肪类型会影响发育。 对于我们NSERC计划的第一部分，我们希望通过使用啮齿动物模型进行一系列实验来确定饮食中PUFA的最佳平衡，以确保最佳的T细胞功能和免疫发育。据认为，PUFA可能通过改变细胞膜中脂质的组成和/或含量来影响T细胞功能。 质膜脂肪的变化究竟如何改变T细胞功能尚未确定，这是我NSERC计划第二部分的重点。 我们将研究细胞膜的特殊部分，称为“脂质筏”。 脂筏参与产生指导T细胞功能的信号传导信息。 我们建议研究脂筏的脂肪组成的变化如何影响细胞中产生的信息，以及最终如何指导细胞的功能。我们的研究将提供对饮食中脂肪对生命早期T细胞基本功能的作用的基本理解，并将有助于确定脂肪酸需求，以优化婴儿的免疫健康。

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.