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<p>Acute liver injury often progresses to liver failure, with immune responses playing a critical role in regulating the inflammatory process. In this study, we aim to investigate the effects of iron on CD11c<sup>+</sup> myeloid cells during acetaminophen-induced liver injury. Iron overload caused by F-box and leucine-rich repeat protein 5 (FBXL5) deficiency in CD11c<sup>+</sup> cells exacerbates liver damage. CD11c<sup>+</sup> myeloid cell-specific FBXL5-deficient mice exhibit higher serum transaminase levels, liver injury, and mortality than the controls. These phenotypes are associated with enhanced neutrophil infiltration and expression of interleukin (IL)-6, a pro-inflammatory cytokine. Mechanistically, iron overload in FBXL5-deficient cells increases IL-6 production by facilitating the recruitment of nuclear factor-κB to the <i>Il-6</i> promoter. In vivo, IL-6 neutralization mitigates liver injury, confirming its role in disease progression. Our findings highlight the role of iron in immune responses and suggest that targeting iron may represent a potential therapeutic strategy for liver injury.</p><p></p>

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Iron overload in CD11c+ myeloid cells exacerbates acetaminophen hepatotoxicity

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月21日

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  • Saisai Liu,
  • Yohei Kanamori,
  • Yudai Ohta,
  • Shuran Li,
  • Yanliang Liu,
  • Hao Li,
  • Mohamed Fathi Saleh,
  • Akihiro Nita,
  • Keiichi I. Nakayama,
  • Toshiro Moroishi

摘要

Acute liver injury often progresses to liver failure, with immune responses playing a critical role in regulating the inflammatory process. In this study, we aim to investigate the effects of iron on CD11c+ myeloid cells during acetaminophen-induced liver injury. Iron overload caused by F-box and leucine-rich repeat protein 5 (FBXL5) deficiency in CD11c+ cells exacerbates liver damage. CD11c+ myeloid cell-specific FBXL5-deficient mice exhibit higher serum transaminase levels, liver injury, and mortality than the controls. These phenotypes are associated with enhanced neutrophil infiltration and expression of interleukin (IL)-6, a pro-inflammatory cytokine. Mechanistically, iron overload in FBXL5-deficient cells increases IL-6 production by facilitating the recruitment of nuclear factor-κB to the Il-6 promoter. In vivo, IL-6 neutralization mitigates liver injury, confirming its role in disease progression. Our findings highlight the role of iron in immune responses and suggest that targeting iron may represent a potential therapeutic strategy for liver injury.