Impact of phytochemicals on epigenetic regulation of cytokine gene expression and immune cell function

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The immune system is responsible for defending against infection by disease-causing microorganisms and eliminating spontaneously-arising cancer cells; however, inappropriate activation of the immune system can lead to potentially harmful uncontrolled inflammation. Interestingly, fruits, vegetables, spices, and some beverages contain a number of potent inflammation-inhibiting substances belonging to a family of plant-derived chemicals known as dietary phytochemicals or phytonutrients. Diets that are rich in phytochemicals are believed to reduce potentially harmful inflammatory responses, at least in part by reducing the production of inflammation-inducing chemical messengers known as cytokines by various cells of the immune system. The mechanism(s) by which these dietary phytochemicals regulate inflammation-promoting cytokine production are not well understood. On the basis of recent evidence that certain dietary phytochemicals are able to modify DNA and thereby regulate the expression of cancer cell genes, we propose that the same epigenetic processes allow certain phytochemicals and/or their major metabolites to control cytokine production by immune cells. Mice are commonly used as a source of immune cells with which to study the molecular basis of processes involved in human immune cell function. We will therefore use a mouse model system to determine the effect of a panel of representative phytonutrients and their major metabolites on the expression and activation of DNA-modifying enzymes in cytokine-producing cells of the innate immune system (macrophages, dendritic cells) and adaptive immune system (T cells). We anticipate that our results will demonstrate a causal effect on inflammation-promoting and inflammation-inhibiting cytokine synthesis by these immune cells. This fundamental immunology research will yield new information on the potential impact of a phytochemical-rich diet on innate and adaptive immune cell function, and inform future studies on the impact of dietary phytochemicals and their major metabolites on immune cell function in vitro and in vivo.