Understanding Phagocytosis Within the Adipose Tissue

项目摘要/摘要 每天，我们周转数十亿个被吞噬细胞移除的凋亡细胞，例如 巨噬细胞。细胞死亡和吞噬清除过程对维持体内平衡至关重要， 与许多疾病的病理有关。据报道，脂肪组织经历了基础周转，并在 在肥胖的情况下，在老鼠和人类中，凋亡的脂肪细胞已经被证明是增加的。这种细胞死亡和 随后巨噬细胞的渗透以清除死亡的细胞被描述为炎症和 在胰岛素抵抗的发展中起致病作用。这种炎症是由巨噬细胞引起的。 活动，因为耗尽巨噬细胞减少炎症和提高胰岛素敏感性。有趣的是，这些 巨噬细胞耗尽的情况不会导致死亡细胞的积累，这可能表明 吞噬细胞群(S)。除了专业吞噬细胞(如巨噬细胞)外，非专业吞噬细胞 吞噬细胞也存在，如消化道和肺部的上皮细胞，或胚胎期间的间充质细胞。 肢体发育。这些非专业吞噬细胞可以在维持体内平衡方面发挥重要作用，但在 脂肪组织到目前为止还没有被定义为这样的群体。在初步研究的基础上，我们建议调查 脂肪组织中特定的非专业吞噬细胞群，并定义这些细胞如何参与 与肥胖相关的炎症、炎症消退和胰岛素抵抗。PtdSer是一种特定的脂质 暴露在凋亡细胞表面，被吞噬细胞用来清除。让我们更好地 操纵这些细胞群的吞噬活性，我们还将研究 磷脂酰丝氨酸(PtdSer)受体。了解细胞类型、吞噬过程和分子成员 在动态平衡和脂肪组织炎症期间，将为肥胖提供重要的治疗机会。

PROJECT SUMMARY/ABSTRACT On a daily basis, we turnover billions of apoptotic cells that are removed by phagocytic cells, such as macrophages. The processes of cell death and phagocytic clearance are vital to maintaining homeostasis and are related to many disease pathologies. The adipose tissue has been reported to undergo basal turnover, and during conditions of obesity, apoptotic adipocytes have been shown to increase in mice and humans. This cell death and subsequent macrophage infiltration to clear the dying cells has been described as a key inducer of inflammation and causative in the development of insulin resistance. This inflammation has been specifically attributed to macrophage activity, as depletion of macrophages reduces inflammation and improves insulin sensitivity. Interestingly, these macrophage depletion conditions do not result in the accumulation of dead cells, possibly demonstrating additional phagocytic population(s). In addition to professional phagocytes (such as macrophages), non-professional phagocytes also exist, such as epithelial cells in the digestive tract and lung, or mesenchymal cells during embryonic limb development. These non-professional phagocytes can play vital roles in maintaining homeostasis, yet in the adipose tissue no such population has been defined thus far. Based on preliminary studies, we propose to investigate specific non-professional phagocytic cell populations in the adipose tissue and define how these cells contribute to inflammation, inflammation resolution, and insulin resistance associated with obesity. PtdSer is a lipid specifically exposed on the surface of apoptotic cells and is used by phagocytic cells for clearance. To allows us to better manipulate the phagocytic activity of these cell populations, we will additionally investigate the role of phosphatidylserine (PtdSer) receptors. Understanding cell types, the phagocytic process, and molecular players during homeostasis and adipose tissue inflammation will provide important therapeutic opportunities for obesity.