Mechanisms linking choline metabolism and immunity

细胞新陈代谢和免疫是两个对生存至关重要的过程。有充分的证据表明，在感染期间，关键的新陈代谢过程会受到影响。然而，新陈代谢的变化会在多大程度上改变免疫系统仍然是个谜。近年来，这些重要过程之间的联系已经成为免疫代谢的新领域。 胆碱是人类从饮食中获得的一种基本营养物质。它是主要类型磷脂的关键成分，磷脂是构成细胞膜的物质，对细胞代谢的许多方面都是基本的。由于胆碱的分子性质，胆碱必须通过特殊的蛋白质转运体进入细胞，其中有两种类型。有机阳离子转运蛋白是一类允许摄取各种分子的蛋白质家族，而胆碱转运蛋白样蛋白(CTL)家族被证明是胆碱高度特异的家族。特别是，我们之前的研究表明，CTL1可以将胆碱运输到称为巨噬细胞的重要免疫细胞中；然而，对于这种情况如何发生、何时发生以及为什么发生，还缺乏完整的了解。 拟议的研究计划旨在了解有助于或阻碍免疫反应的代谢途径，并研究胆碱摄取和代谢指导免疫代谢程序的机制。我们将使用一种新的基因小鼠模型，这种模型已经被专门设计为缺乏CTL1蛋白，以及一种有效和特定的药物来阻止胆碱的摄取。这些特定的研究工具，加上我们在分子/细胞生物学和免疫代谢方面的专业知识，将确保我们实现我们的目标。 我们的研究将填补新陈代谢和免疫过程之间分子相互作用的理解空白。我们的目标是促进对重要的营养胆碱和脂类代谢如何最终调节免疫代谢的了解。

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.