Scholarlink

<p>The lung is highly vulnerable to inflammatory injury during sepsis, and acute lung injury (ALI) is a major cause of mortality in critically ill patients. Pyroptosis amplifies immune responses by promoting the release of inflammatory cytokines, and Z-DNA binding protein 1 (ZBP1) has emerged as a key upstream regulator of programmed cell death and inflammatory signaling. Nevertheless, the contribution of ZBP1 to human sepsis-induced ALI and its associated cellular programs remains poorly defined. Here, by integrating single-cell RNA sequencing data from bronchoalveolar lavage fluid (BALF) of patients with sepsis-induced ALI and from septic mouse lungs, we identified a distinct subset of pyroptosis-associated macrophages that expands during disease progression and exhibits ZBP1-dependent inflammasome activation. ZBP1 activation promoted inflammasome assembly, induced macrophage pyroptosis, and released pro-inflammatory mediators that impaired mitochondrial function and barrier integrity of alveolar type II (AT2) epithelial cells. ZBP1 deficiency markedly attenuated macrophage-AT2 inflammatory signaling and reduced the inflammatory amplification loop. Collectively, these findings identify ZBP1-mediated macrophage pyroptosis as a critical mechanism driving epithelial dysfunction during sepsis-induced ALI and provide a rationale for developing ZBP1-targeted strategies to restore immune–epithelial homeostasis and prevent organ failure in sepsis.</p><p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

ZBP1-driven pyroptosis-associated alveolar macrophages exacerbate epithelial dysfunction in sepsis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年6月26日

查看全文
  • Feicheng Zhou,
  • Haolin Tian,
  • Haixia Wang,
  • Hongxiang Huang,
  • Xuwei Lin,
  • Yuanyuan Zhao,
  • Huaijun Chen,
  • Ting Gong

摘要

The lung is highly vulnerable to inflammatory injury during sepsis, and acute lung injury (ALI) is a major cause of mortality in critically ill patients. Pyroptosis amplifies immune responses by promoting the release of inflammatory cytokines, and Z-DNA binding protein 1 (ZBP1) has emerged as a key upstream regulator of programmed cell death and inflammatory signaling. Nevertheless, the contribution of ZBP1 to human sepsis-induced ALI and its associated cellular programs remains poorly defined. Here, by integrating single-cell RNA sequencing data from bronchoalveolar lavage fluid (BALF) of patients with sepsis-induced ALI and from septic mouse lungs, we identified a distinct subset of pyroptosis-associated macrophages that expands during disease progression and exhibits ZBP1-dependent inflammasome activation. ZBP1 activation promoted inflammasome assembly, induced macrophage pyroptosis, and released pro-inflammatory mediators that impaired mitochondrial function and barrier integrity of alveolar type II (AT2) epithelial cells. ZBP1 deficiency markedly attenuated macrophage-AT2 inflammatory signaling and reduced the inflammatory amplification loop. Collectively, these findings identify ZBP1-mediated macrophage pyroptosis as a critical mechanism driving epithelial dysfunction during sepsis-induced ALI and provide a rationale for developing ZBP1-targeted strategies to restore immune–epithelial homeostasis and prevent organ failure in sepsis.