Modulation of T cell function through manipulation of fatty acids

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The overall goal of my NSERC program is to establish the mechanisms by which dietary polyunsaturated fatty acids (PUFA) modulate immunity.  The T lymphocyte is a key component of the immune system and its function changes over the lifecycle.  These cells become important to the individual/animal when challenged by their external (i.e. pathogens, dietary antigens, microflora) or internal (i.e. physiological aging) environments.  To determine the importance of diet fat on T cell function it becomes necessary to challenge T cells using stimuli (e.g. mitogens, bacterial antigens, hormones, cytokines) representative of 'normal' physiological challenges.  Our research has demonstrated that both the level of fat and the balance between n-6 PUFA and n-3 PUFA in the diet modulate (beneficially or negatively) T cell function.  Using rodent models we propose to determine the balance of PUFA necessary to optimize T cell function across the lifespan.  Many of the mechanisms proposed to explain the effect of fatty acids on T cell function begin with changes in the composition or content of fats in the membrane.  Exactly how a change in plasma membrane lipids alters T cell function has not been established and is the second part of my NSERC program.  Distinct microdomains in the plasma membrane called 'lipid rafts' have recently been identified.  These are involved in signaling processes that direct the physiological function of T cells.  In T cells, many important receptors and signaling proteins are either constitutively located in the lipid rafts or upon activation move into rafts.  Our data and that of others suggest that changes in fatty acids in the raft can change the amount and function of important molecules in these rafts.  To date, studies in this area have been limited to cell lines or to cells isolated from animals with cancer.  The effect of diet fat on T cell raft composition from healthy animals is not known.  These studies will provide a fundamental understanding of the role of fatty acids on the function of T cells across the lifespan.