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<p>Sepsis-induced acute lung injury (ALI) involves a complex interplay between immune cells and the pulmonary endothelium. However, the molecular regulators that coordinate this interaction remain poorly defined. In a murine sepsis model, we identified a subset of lung-resident macrophages characterized by robust IL-1β expression as pivotal contributors to lung damage. Single-cell RNA sequencing (scRNA-seq) delineated a distinct IL-1β⁺ macrophage population with pronounced pro-inflammatory transcriptional features and enhanced endothelial communication. These macrophages exhibited intensified ligand–receptor interactions with pulmonary endothelial cells, corresponding with elevated vascular leakage and histopathological evidence of injury. Immunoassays, Western blotting, and histopathology confirmed IL-1β upregulation during lung injury. Furthermore, metabolomics and in vitro co-culture experiments demonstrated that IL-1β impairs endothelial integrity and modulates metabolic activity. This study reveals a novel immune-metabolic axis whereby IL-1β<sup>+</sup> macrophages orchestrate endothelial dysfunction and tissue injury in sepsis. Our findings highlight IL-1β as a potential therapeutic target for mitigating ALI in septic patients.</p><p></p>

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IL-1β+ lung-resident macrophages mediate endothelial dysfunction and acute lung injury in sepsis through immune-metabolic crosstalk

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月8日

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  • Yang Dong,
  • Tianyuan Li,
  • Bei Fang,
  • Dingde Long,
  • Ying Tian,
  • Huan Fu

摘要

Sepsis-induced acute lung injury (ALI) involves a complex interplay between immune cells and the pulmonary endothelium. However, the molecular regulators that coordinate this interaction remain poorly defined. In a murine sepsis model, we identified a subset of lung-resident macrophages characterized by robust IL-1β expression as pivotal contributors to lung damage. Single-cell RNA sequencing (scRNA-seq) delineated a distinct IL-1β⁺ macrophage population with pronounced pro-inflammatory transcriptional features and enhanced endothelial communication. These macrophages exhibited intensified ligand–receptor interactions with pulmonary endothelial cells, corresponding with elevated vascular leakage and histopathological evidence of injury. Immunoassays, Western blotting, and histopathology confirmed IL-1β upregulation during lung injury. Furthermore, metabolomics and in vitro co-culture experiments demonstrated that IL-1β impairs endothelial integrity and modulates metabolic activity. This study reveals a novel immune-metabolic axis whereby IL-1β+ macrophages orchestrate endothelial dysfunction and tissue injury in sepsis. Our findings highlight IL-1β as a potential therapeutic target for mitigating ALI in septic patients.