A-Gonzalez Noelia, Quintana Juan A, García-Silva Susana, Mazariegos Marina, González de la Aleja Arturo, Nicolás-Ávila José A, Walter Wencke, Adrover Jose M, Crainiciuc Georgiana, Kuchroo Vijay K, Rothlin Carla V, Peinado Héctor, Castrillo Antonio, Ricote Mercedes, Hidalgo Andrés
Area of Cell and Developmental Biology, Centro Nacional de Investigaciones Cardiovasculares Carlos III, 28029 Madrid, Spain.
Microenvironment and Metastasis Group, Molecular Oncology Program, Spanish National Cancer Research Centre, 28029 Madrid, Spain.
J Exp Med. 2017 May 1;214(5):1281-1296. doi: 10.1084/jem.20161375. Epub 2017 Apr 21.
Tissue-resident macrophages display varying phenotypic and functional properties that are largely specified by their local environment. One of these functions, phagocytosis, mediates the natural disposal of billions of cells, but its mechanisms and consequences within living tissues are poorly defined. Using a parabiosis-based strategy, we identified and isolated macrophages from multiple tissues as they phagocytosed blood-borne cellular material. Phagocytosis was circadianally regulated and mediated by distinct repertoires of receptors, opsonins, and transcription factors in macrophages from each tissue. Although the tissue of residence defined the core signature of macrophages, phagocytosis imprinted a distinct antiinflammatory profile. Phagocytic macrophages expressed CD206, displayed blunted expression of , and supported tissue homeostasis. Thus, phagocytosis is a source of macrophage heterogeneity that acts together with tissue-derived factors to preserve homeostasis.
组织驻留巨噬细胞表现出不同的表型和功能特性，这些特性在很大程度上由其局部环境决定。其中一项功能，即吞噬作用，介导了数十亿细胞的自然清除，但其在活组织中的机制和后果仍不清楚。我们采用基于联体生活的策略，在巨噬细胞吞噬血源细胞物质时，从多个组织中识别并分离出巨噬细胞。吞噬作用受昼夜节律调节，且由每个组织的巨噬细胞中不同的受体、调理素和转录因子库介导。尽管驻留组织定义了巨噬细胞的核心特征，但吞噬作用赋予了独特的抗炎特征。吞噬性巨噬细胞表达CD206，表现出 的表达减弱，并维持组织稳态。因此，吞噬作用是巨噬细胞异质性的一个来源，它与组织衍生因子共同作用以维持稳态。
