Center for Cardiovascular Research, Division of Cardiology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO, USA.
Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Nat Med. 2018 Aug;24(8):1234-1245. doi: 10.1038/s41591-018-0059-x. Epub 2018 Jun 11.
Paradigm-shifting studies in the mouse have identified tissue macrophage heterogeneity as a critical determinant of immune responses. In contrast, surprisingly little is known regarding macrophage heterogeneity in humans. Macrophages within the mouse heart are partitioned into CCR2- and CCR2+ subsets with divergent origins, repopulation mechanisms, and functions. Here, we demonstrate that the human myocardium also contains distinct subsets of CCR2- and CCR2+ macrophages. Analysis of sex-mismatched heart transplant recipients revealed that CCR2- macrophages are a tissue-resident population exclusively replenished through local proliferation, whereas CCR2+ macrophages are maintained through monocyte recruitment and proliferation. Moreover, CCR2- and CCR2+ macrophages have distinct functional properties, analogous to reparative CCR2- and inflammatory CCR2+ macrophages in the mouse heart. Clinically, CCR2+ macrophage abundance is associated with left ventricular remodeling and systolic function in heart failure patients. Collectively, these observations provide initial evidence for the functional importance of macrophage heterogeneity in the human heart.
在小鼠中进行的范式转变研究表明，组织巨噬细胞异质性是免疫反应的关键决定因素。相比之下，人们对人类巨噬细胞的异质性知之甚少。小鼠心脏中的巨噬细胞分为 CCR2-和 CCR2+亚群，它们具有不同的起源、再群体机制和功能。在这里，我们证明人类心肌中也存在着不同的 CCR2-和 CCR2+巨噬细胞亚群。对性别错配心脏移植受者的分析表明，CCR2-巨噬细胞是一种组织驻留的群体，仅通过局部增殖来补充，而 CCR2+巨噬细胞则通过单核细胞募集和增殖来维持。此外，CCR2-和 CCR2+巨噬细胞具有不同的功能特性，类似于小鼠心脏中的修复性 CCR2-和炎症性 CCR2+巨噬细胞。临床上，CCR2+巨噬细胞的丰度与心力衰竭患者的左心室重构和收缩功能有关。总之，这些观察结果为人类心脏中巨噬细胞异质性的功能重要性提供了初步证据。
