Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, New York, NY
Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, New York, NY.
J Exp Med. 2019 Apr 1;216(4):786-806. doi: 10.1084/jem.20181049. Epub 2019 Mar 12.
Tissue-resident macrophages are the most abundant immune cell population in healthy adipose tissue. Adipose tissue macrophages (ATMs) change during metabolic stress and are thought to contribute to metabolic syndrome. Here, we studied ATM subpopulations in steady state and in response to nutritional and infectious challenges. We found that tissue-resident macrophages from healthy epididymal white adipose tissue (eWAT) tightly associate with blood vessels, displaying very high endocytic capacity. We refer to these cells as vasculature-associated ATMs (VAMs). Chronic high-fat diet (HFD) results in the accumulation of a monocyte-derived CD11cCD64 double-positive (DP) macrophage eWAT population with a predominant anti-inflammatory/detoxifying gene profile, but reduced endocytic function. In contrast, fasting rapidly and reversibly leads to VAM depletion, while acute inflammatory stress induced by pathogens transiently depletes VAMs and simultaneously boosts DP macrophage accumulation. Our results indicate that ATM populations dynamically adapt to metabolic stress and inflammation, suggesting an important role for these cells in maintaining tissue homeostasis.
组织驻留巨噬细胞是健康脂肪组织中最丰富的免疫细胞群体。脂肪组织巨噬细胞（ATMs）在代谢应激期间发生变化，被认为与代谢综合征有关。在这里，我们研究了稳态下和营养及感染挑战下的 ATM 亚群。我们发现，来自健康附睾白色脂肪组织（eWAT）的组织驻留巨噬细胞与血管紧密相关，表现出非常高的内吞能力。我们将这些细胞称为血管相关 ATMs（VAMs）。慢性高脂肪饮食（HFD）导致单核细胞衍生的 CD11cCD64 双阳性（DP）巨噬细胞 eWAT 群体的积累，其具有主要的抗炎/解毒基因谱，但内吞功能降低。相比之下，禁食会迅速且可逆地导致 VAM 耗竭，而病原体引起的急性炎症应激会短暂耗尽 VAMs 并同时增加 DP 巨噬细胞的积累。我们的结果表明，ATM 群体动态适应代谢应激和炎症，表明这些细胞在维持组织稳态方面发挥着重要作用。
