Scholarlink

Background <p>Traumatic brain injury (TBI) causes significant neuronal death, but the underlying mechanisms remain poorly understood. The role of interleukin-23 (IL-23) signaling in post-traumatic neuronal injury requires investigation.</p> Methods <p>We examined IL-23 levels in clinical samples from TBI patients and healthy controls. Using a mouse TBI model, we investigated the effects of IL-23 neutralization and explored the cellular mechanisms through analysis of IL-23 receptor expression, JAK2/STAT3 pathway activation, and macrophage infiltration.</p> Results <p>We found elevated IL-23 levels in both serum and brain tissues of TBI patients. TBI induced neuronal IL-23 receptor expression and activated the JAK2/STAT3 pathway. Infiltrating macrophages were identified as the main IL-23 source, recruited by neuron-derived C-C motif chemokine ligand 2 (CCL2). IL-23 neutralization or CCL2 blockade reduced neuronal ferroptosis and improved neurological outcomes in the mouse model.</p> Conclusions <p>Our findings reveal a novel CCL2-macrophage-IL-23 axis in TBI pathogenesis, where IL-23 promotes neuronal ferroptosis through direct receptor-mediated effects. Targeting this pathway represents a potential therapeutic strategy for TBI treatment.</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

IL-23 promotes neuronal ferroptosis via IL-23R/STAT3 signaling after traumatic brain injury

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月1日

查看全文
  • Bo Chen,
  • Guihong Shi,
  • Jianye Xu,
  • Xu Zhang,
  • Yanlin Zhu,
  • Lei Li,
  • Cong Wang,
  • Dilmurat Gheyret,
  • Jinchao Wang,
  • Xilei Liu,
  • Yiyao Cao,
  • Rui Tan,
  • Yuan Zhou,
  • RongCai Jiang,
  • Shenghui Li,
  • Tuo Li,
  • Xiao Liu,
  • Xin Chen,
  • Guili Yang,
  • Jianning Zhang,
  • Shu Zhang

摘要

Background

Traumatic brain injury (TBI) causes significant neuronal death, but the underlying mechanisms remain poorly understood. The role of interleukin-23 (IL-23) signaling in post-traumatic neuronal injury requires investigation.

Methods

We examined IL-23 levels in clinical samples from TBI patients and healthy controls. Using a mouse TBI model, we investigated the effects of IL-23 neutralization and explored the cellular mechanisms through analysis of IL-23 receptor expression, JAK2/STAT3 pathway activation, and macrophage infiltration.

Results

We found elevated IL-23 levels in both serum and brain tissues of TBI patients. TBI induced neuronal IL-23 receptor expression and activated the JAK2/STAT3 pathway. Infiltrating macrophages were identified as the main IL-23 source, recruited by neuron-derived C-C motif chemokine ligand 2 (CCL2). IL-23 neutralization or CCL2 blockade reduced neuronal ferroptosis and improved neurological outcomes in the mouse model.

Conclusions

Our findings reveal a novel CCL2-macrophage-IL-23 axis in TBI pathogenesis, where IL-23 promotes neuronal ferroptosis through direct receptor-mediated effects. Targeting this pathway represents a potential therapeutic strategy for TBI treatment.