Scholarlink

<p>The imbalance in macrophage M1/M2 polarization is a critical driver of excessive inflammation during the early stage of acute lung injury/acute respiratory distress syndrome (ALI/ARDS), yet its upstream regulatory mechanisms remain incompletely understood. In this study, we investigated the role of interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) in early ALI pathogenesis. IFIT3 was significantly upregulated in pulmonary macrophages from ALI mice. Functionally, IFIT3 promoted M1 polarization and exacerbated lung inflammatory injury by positively regulating the cGAS-STING pathway. Mechanistically, IFIT3 served as a molecular bridge between STING and the deubiquitinase USP18, thereby inhibiting ubiquitination-mediated degradation of STING and amplifying downstream inflammatory signaling. Furthermore, IFIT3 knockdown ameliorated early lung injury in vivo. In conclusion, our findings demonstrate that IFIT3 promotes macrophage M1 polarization and early inflammation in ALI by scaffolding USP18 to stabilize STING, suggesting its potential as a therapeutic target for ALI/ARDS.</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

IFIT3 stabilizes STING via USP18 to drive M1 macrophage polarization and early inflammation in acute lung injury

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月13日

查看全文
  • Nana Tang,
  • Yang Yang,
  • Yuanyuan Zeng,
  • Jianjie Zhu,
  • Jianjun Li,
  • Jiajia Wang,
  • Ling Ding,
  • Jian-an Huang,
  • Zeyi Liu

摘要

The imbalance in macrophage M1/M2 polarization is a critical driver of excessive inflammation during the early stage of acute lung injury/acute respiratory distress syndrome (ALI/ARDS), yet its upstream regulatory mechanisms remain incompletely understood. In this study, we investigated the role of interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) in early ALI pathogenesis. IFIT3 was significantly upregulated in pulmonary macrophages from ALI mice. Functionally, IFIT3 promoted M1 polarization and exacerbated lung inflammatory injury by positively regulating the cGAS-STING pathway. Mechanistically, IFIT3 served as a molecular bridge between STING and the deubiquitinase USP18, thereby inhibiting ubiquitination-mediated degradation of STING and amplifying downstream inflammatory signaling. Furthermore, IFIT3 knockdown ameliorated early lung injury in vivo. In conclusion, our findings demonstrate that IFIT3 promotes macrophage M1 polarization and early inflammation in ALI by scaffolding USP18 to stabilize STING, suggesting its potential as a therapeutic target for ALI/ARDS.