Distinct macrophage populations direct inflammatory versus physiological changes in adipose tissue
Distinct macrophage populations direct inflammatory versus physiological changes in adipose tissue
复制标题
DOI：
10.1073/pnas.1802611115
复制
发表时间：
2018-05-29
影响因子：
11.1
通讯作者：
Lazar, Mitchell A.
中科院分区：
文献类型：
--
作者：
Hill, David A.;Lim, Hee-Woong;Lazar, Mitchell A.
肥胖的特征是脂肪中巨噬细胞的积累，其中一些巨噬细胞在脂肪细胞周围形成独特的冠状结构（CLS）。虽然人们认为存在多个离散的脂肪组织巨噬细胞 (ATM) 子集，但它们各自对脂肪组织的影响以及构成 ATM 子集功能差异的转录机制尚不清楚。我们报告说，小鼠和人类的肥胖脂肪组织含有多个不同的 ATM 群体，具有独特的组织分布、转录组、染色质景观和功能。小鼠 Ly6c ATM 位于 CLS 外部，具有脂肪生成作用，而 CD9 ATM 位于 CLS 内，富含脂质，具有促炎作用。将 Ly6c ATM 过继转移到瘦小鼠体内会激活正常脂肪细胞生理学的典型基因程序。相比之下，CD9 ATM 的过继转移驱动基因表达，这是肥胖的特征。重要的是，人类脂肪组织含有类似的 ATM 群体，包括随体重增加而增加的脂质 CD9 ATM。这些结果提供了 ATM 内细胞和功能异质性的更高分辨率，并提供了开发新的免疫导向疗法来治疗肥胖和相关后遗症的框架。
Obesity is characterized by an accumulation of macrophages in adipose, some of which form distinct crown-like structures (CLS) around fat cells. While multiple discrete adipose tissue macrophage (ATM) subsets are thought to exist, their respective effects on adipose tissue, and the transcriptional mechanisms that underlie the functional differences between ATM subsets, are not well understood. We report that obese fat tissue of mice and humans contain multiple distinct populations of ATMs with unique tissue distributions, transcriptomes, chromatin landscapes, and functions. Mouse Ly6c ATMs reside outside of CLS and are adipogenic, while CD9 ATMs reside within CLS, are lipid-laden, and are proinflammatory. Adoptive transfer of Ly6c ATMs into lean mice activates gene programs typical of normal adipocyte physiology. By contrast, adoptive transfer of CD9 ATMs drives gene expression that is characteristic of obesity. Importantly, human adipose tissue contains similar ATM populations, including lipid-laden CD9 ATMs that increase with body mass. These results provide a higher resolution of the cellular and functional heterogeneity within ATMs and provide a framework within which to develop new immune-directed therapies for the treatment of obesity and related sequela.