The lung is constantly exposed to airborne pathogens and particles that can cause alveolar damage. Hence, appropriate repair responses are essential for gas exchange and life. Here, we deciphered the spatiotemporal trajectory and function of an atypical population of macrophages after lung injury. Post–influenza A virus (IAV) infection, short-lived monocyte-derived Ly6G-expressing macrophages (Ly6G + Macs) were recruited to the alveoli of lung perilesional areas. Ly6G + Macs engulfed immune cells, exhibited a high metabolic potential, and clustered with alveolar type 2 epithelial cells (AT2s) in zones of active epithelial regeneration. Ly6G + Macs were partially dependent on granulocyte-macrophage colony-stimulating factor and interleukin-4 receptor signaling and were essential for AT2-dependent alveolar regeneration. Similar macrophages were recruited in other models of injury and in the airspaces of lungs from patients with suspected pneumonia. This study identifies perilesional alveolar Ly6G + Macs as a spatially restricted, short-lived macrophage subset promoting epithelial regeneration postinjury, thus representing an attractive therapeutic target for treating lung damage.

中文翻译：

---

招募非典型 Ly6G + 巨噬细胞许可肺损伤后肺泡再生


肺部不断暴露于空气中的病原体和颗粒，可能导致肺泡损伤。因此，适当的修复反应对于气体交换和生命至关重要。在这里，我们破译了肺损伤后非典型巨噬细胞群的时空轨迹和功能。甲型流感病毒 (IAV) 感染后，短命的单核细胞衍生的表达 Ly6G 的巨噬细胞 (Ly6G + Macs) 被募集到肺病灶周围区域的肺泡中。 Ly6G + Macs 吞噬免疫细胞，表现出高代谢潜力，并在活跃的上皮再生区域与肺泡 2 型上皮细胞 (AT2s) 聚集。 Ly6G + Macs 部分依赖于粒细胞巨噬细胞集落刺激因子和白细胞介素 4 受体信号传导，对于 AT2 依赖性肺泡再生至关重要。在其他损伤模型和疑似肺炎患者的肺腔中也招募了类似的巨噬细胞。这项研究将病灶周围的肺泡 Ly6G + Macs 确定为一种空间受限、寿命短的巨噬细胞亚群，可促进损伤后上皮再生，因此代表了治疗肺损伤的一个有吸引力的治疗靶点。