Mechanisms linking choline metabolism and immunity

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Cellular metabolism and immunity are two processes that are critical for survival. It has been well documented that during infection, key metabolic processes are affected. However, the extent to which changes in metabolism could alter the immune system has remained a mystery. In recent years, the links between these important processes have emerged as the novel field of immunometabolism.***Choline is an essential nutrient that humans obtain from their diets. It is the critical component of the major type of phospholipid, which is what makes up cellular membranes and is fundamental to many aspects of cellular metabolism. Due to its molecular properties, choline must be transported into the cell via specialized protein transporters, of which there are two types. Organic cation transporters are a family of proteins that allow the uptake of various molecules, whereas the choline transporter-like (CTL) family of proteins has been shown to be highly specific for choline. In particular, our previous research has shown that CTL1 can transport choline into important immune cells called macrophages; however, a complete understanding of how, when and why this happens is lacking. ***The proposed research program aims to understand the metabolic pathways that help or hinder immune responses and to study the mechanisms by which choline uptake and metabolism direct programs in immunometabolism. We will use a new genetic mouse model that has been specifically engineered to lack the CTL1 protein, as well as a potent and specific drug that blocks choline uptake. These specific research tools coupled with our expertise in molecular/cell biology and immunometabolism will ensure that we meet our objectives.***Our research will fill a gap in the understanding of molecular interactions between metabolic and immune processes. We aim to advance knowledge of how the important nutrient choline, and the metabolism of lipids, can ultimately regulate immunometabolism. ************