Mechanisms linking choline metabolism and immunity

细胞代谢和免疫是对生存至关重要的两个过程。已有文献表明，在感染期间，关键的代谢过程受到影响。然而，新陈代谢的变化能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成为免疫代谢的新领域。***胆碱是人类从饮食中获得的一种必需营养素。它是主要类型磷脂的关键成分，磷脂构成细胞膜，是细胞代谢的许多方面的基础。由于其分子性质，胆碱必须通过专门的蛋白质转运体转运到细胞中，其中有两种类型。有机阳离子转运蛋白是一种允许摄取各种分子的蛋白质家族，而胆碱转运蛋白样（CTL）家族已被证明对胆碱具有高度特异性。特别是，我们之前的研究表明，CTL1可以将胆碱转运到称为巨噬细胞的重要免疫细胞中；然而，对于这种情况是如何、何时以及为什么发生的，我们还缺乏完整的理解。***本研究计划旨在了解帮助或阻碍免疫反应的代谢途径，并研究胆碱摄取和代谢直接影响免疫代谢的机制。我们将使用一种新的遗传小鼠模型，该模型经过专门设计，缺乏CTL1蛋白，以及一种阻断胆碱摄取的强效特异性药物。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。我们的研究将填补对代谢和免疫过程之间分子相互作用理解的空白。我们的目标是推进对重要营养物质胆碱和脂质代谢如何最终调节免疫代谢的认识。************

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. ************