Lysosomes have a central role in the disposal of extracellular and intracellular cargo and also function as metabolic sensors and signalling platforms in the immunometabolic reprogramming of macrophages and other immune cells in atherosclerosis. Lysosomes can rapidly sense the presence of nutrients within immune cells, thereby switching from catabolism of extracellular material to the recycling of intracellular cargo. Such a fine-tuned degradative response supports the generation of metabolic building blocks through effectors such as mTORC1 or TFEB. By coupling nutrients to downstream signalling and metabolism, lysosomes serve as a crucial hub for cellular function in innate and adaptive immune cells. Lysosomal dysfunction is now recognized to be a hallmark of atherogenesis. Perturbations in nutrient-sensing and signalling have profound effects on the capacity of immune cells to handle cholesterol, perform phagocytosis and efferocytosis, and limit the activation of the inflammasome and other inflammatory pathways. Strategies to improve lysosomal function hold promise as novel modulators of the immunoinflammatory response associated with atherosclerosis. In this Review, we describe the crosstalk between lysosomal biology and immune cell function and polarization, with a particular focus on cellular immunometabolic reprogramming in the context of atherosclerosis.

溶酶体在细胞外和细胞内货物的处理中起着核心作用，并且在动脉粥样硬化中巨噬细胞和其他免疫细胞的免疫代谢重编程中也起着代谢传感器和信号平台的作用。溶酶体可以快速感知免疫细胞内营养物质的存在，从而从细胞外物质的分解代谢转变为细胞内货物的回收。这种微调的降解反应支持通过 mTORC1 或 TFEB 等效应子产生代谢构建块。通过将营养物质与下游信号传导和代谢相结合，溶酶体成为先天性和适应性免疫细胞中细胞功能的关键枢纽。溶酶体功能障碍现在被认为是动脉粥样硬化形成的标志。营养感应和信号传导的扰动对免疫细胞处理胆固醇、进行吞噬作用和胞吞作用以及限制炎性小体和其他炎症途径的激活能力有深远影响。改善溶酶体功能的策略有望成为与动脉粥样硬化相关的免疫炎症反应的新型调节剂。在这篇综述中，我们描述了溶酶体生物学与免疫细胞功能和极化之间的串扰，特别关注动脉粥样硬化背景下的细胞免疫代谢重编程。