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

免疫系统负责抵御致病微生物的感染，并消除自发产生的癌细胞；然而，不适当的免疫系统激活可能导致潜在的有害的不受控制的炎症。有趣的是，水果、蔬菜、香料和一些饮料中含有许多有效的炎症抑制物质，这些物质属于植物衍生的化学物质家族，被称为膳食植物化学物质或植物营养素。富含植物化学物质的饮食被认为可以减少潜在的有害炎症反应，至少在一定程度上是通过减少免疫系统中各种细胞产生的炎症诱导化学信使——细胞因子。这些膳食植物化学物质调节促炎细胞因子产生的机制尚不清楚。根据最近的证据，某些膳食植物化学物质能够修饰DNA，从而调节癌细胞基因的表达，我们提出相同的表观遗传过程允许某些植物化学物质和/或其主要代谢物控制免疫细胞的细胞因子产生。小鼠通常被用作研究人类免疫细胞功能过程的分子基础的免疫细胞来源。因此，我们将使用小鼠模型系统来确定一组具有代表性的植物营养素及其主要代谢物对先天免疫系统（巨噬细胞、树突状细胞）和适应性免疫系统（T细胞）细胞因子产生细胞中dna修饰酶的表达和激活的影响。我们预计我们的结果将证明这些免疫细胞对炎症促进和炎症抑制细胞因子合成的因果效应。这项基础免疫学研究将提供关于富含植物化学物质的饮食对先天和适应性免疫细胞功能潜在影响的新信息，并为未来关于饮食中植物化学物质及其主要代谢物对体外和体内免疫细胞功能影响的研究提供信息。

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.