Programing of T cell function and development through the manipulation of dietary fat in the early postnatal period

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The overall goal of my NSERC program is to establish the mechanisms by which dietary lipids modulate T cell function and development. T cells are important to the individual/animal when they are challenged by their external (i.e. pathogens, dietary antigens, microflora) or internal (i.e. physiological aging) environments. T cells develops primarily during the suckling and the early weaning period; however, the role of the maternal and infant diet on this process has not been established. An important T-cell mediated processes that occurs early in life is the development of oral tolerance (OT); the ability to distinguish between harmful and harmless oral antigens. Epidemiological studies have found that consumption of n-3 long chain polyunsaturated fatty acids (LCPUFA) early in life reduce the risk of atopic diseases (failure to develop OT). Our research, has demonstrated that the maternal intake of n-3 LCPUFA and phosphatidylcholine (PC), programs T cell function in their offspring. The goal of my NSERC Discovery Grant is to establish the mechanisms by which dietary LCPUFA and PC modulate T cell function and development of OT. More specifically my aims are to: 1) determine the optimal dose and timing (critical window) for feeding LCPUFA/PC to support immune development and establishment of OT and 2) determine the mechanism(s) for the effect of dietary LCPUFA/PC on T cell function and OT and 3) optimize the dietary lipid composition of the maternal diet so as to facilitate immune development and establishment of OT. To understand these developmental immunological functions we will feed nutritionally adequate diets differing only in the lipids of interest to lactating dams (and later in a cross over model to the pups) and examine the effects on immune development at weaning and later in life. The ability to develop tolerance, OT will be induced in the pups using two methodologies that induce either systemic or mucosal tolerance to the food protein Ovalbumin (OVA). Immune cells will be isolated from spleen, mesenteric lymph nodes (MLN) and Peyers Patches (PP) and characterized (by flow cytometry) and used to assess their ability to respond to ‘normal physiological challenges’ determined by stimulating them with mitogens and food proteins. Using isolated immune cells from various regions of the body we will establish the mechanism for the diet effects by measuring the change in fatty acid composition and amount of phospholipids (lipidomics) and the amount of raft-associated proteins (T cell receptor, CD4, CD28, LAT, Lck, Fyn, Lyn, CTLA-4, PLCγ1) involved in responding to Ag and establishing OT My NSERC program will provide a fundamental understanding of the role of dietary fats during critical periods of T development and contribute to the unique training of a number of different types of HPQ in the growing field of nutritional immunology.