Gibbings Sophie L, Goyal Rajni, Desch A Nicole, Leach Sonia M, Prabagar Miglena, Atif Shaikh M, Bratton Donna L, Janssen William, Jakubzick Claudia V
Department of Pediatrics.
Department of Immunology and Microbiology.
Blood. 2015 Sep 10;126(11):1357-66. doi: 10.1182/blood-2015-01-624809. Epub 2015 Jul 31.
Alveolar macrophages (AMs) reside on the luminal surfaces of the airways and alveoli where they maintain host defense and promote alveolar homeostasis by ingesting inhaled particulates and regulating inflammatory responses. Recent studies have demonstrated that AMs populate the lungs during embryogenesis and self-renew throughout life with minimal replacement by circulating monocytes, except under extreme conditions of depletion or radiation injury. Here we demonstrate that on a global scale, environment appears to dictate AM development and function. Indeed, transcriptome analysis of embryonic host-derived and postnatal donor-derived AMs coexisting within the same mouse demonstrated >98% correlation and overall functional analyses were similar. However, we also identified several genes whose expression was dictated by origin rather than environment. The most differentially expressed gene not altered by environment was Marco, a gene recently demonstrated to have enhancer activity in embryonic-derived but not postnatal-derived tissue macrophages. Overall, we show that under homeostatic conditions, the environment largely dictates the programming and function of AMs, whereas the expression of a small number of genes remains linked to the origin of the cell.
肺泡巨噬细胞（AMs）驻留在气道和肺泡的管腔表面，通过摄取吸入的颗粒物质和调节炎症反应来维持宿主防御并促进肺泡内环境稳定。最近的研究表明，AMs在胚胎发育过程中定居于肺部，并在一生中自我更新，除了在极度耗竭或辐射损伤的极端情况下，循环单核细胞对其替代极少。在这里，我们证明在全球范围内，环境似乎决定了AMs的发育和功能。事实上，对同一小鼠体内共存的胚胎宿主来源和出生后供体来源的AMs进行转录组分析，显示两者相关性超过98%，且整体功能分析相似。然而，我们也鉴定出了几个基因，其表达由来源而非环境决定。在未受环境改变的情况下，差异表达最显著的基因是Marco，该基因最近被证明在胚胎来源而非出生后来源的组织巨噬细胞中具有增强子活性。总体而言，我们表明在稳态条件下，环境在很大程度上决定了AMs的编程和功能，而少数基因的表达仍与细胞来源相关。
