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

IF 8.2 2区生物学 Q1 CELL BIOLOGY

Cell Communication and Signaling Pub Date : 2025-07-01 DOI:10.1186/s12964-025-02319-4

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

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引用次数: 0

Abstract

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.

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IL-23通过IL-23R/STAT3信号通路促进脑外伤后神经元铁下垂。

背景：外伤性脑损伤（TBI）引起显著的神经元死亡，但其潜在机制尚不清楚。白细胞介素-23 （IL-23）信号在创伤后神经元损伤中的作用有待进一步研究。方法：检测TBI患者和健康对照者临床样本中IL-23水平。我们利用小鼠TBI模型，通过分析IL-23受体表达、JAK2/STAT3通路激活和巨噬细胞浸润，研究IL-23中和的作用，并探讨其细胞机制。结果：我们发现脑外伤患者血清和脑组织中IL-23水平升高。TBI诱导神经元IL-23受体表达，激活JAK2/STAT3通路。浸润性巨噬细胞被确定为IL-23的主要来源，由神经元源性C-C基序趋化因子配体2 （CCL2）募集。在小鼠模型中，IL-23中和或CCL2阻断可减少神经元铁下垂并改善神经预后。结论：我们的研究结果揭示了一种新的ccl2 -巨噬细胞-IL-23轴在TBI发病机制中，IL-23通过直接受体介导的作用促进神经元铁凋亡。靶向这一途径代表了TBI治疗的潜在治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Communication and Signaling CELL BIOLOGY-

CiteScore

11.00

自引率

0.00%

发文量

180

期刊介绍： Cell Communication and Signaling (CCS) is a peer-reviewed, open-access scientific journal that focuses on cellular signaling pathways in both normal and pathological conditions. It publishes original research, reviews, and commentaries, welcoming studies that utilize molecular, morphological, biochemical, structural, and cell biology approaches. CCS also encourages interdisciplinary work and innovative models, including in silico, in vitro, and in vivo approaches, to facilitate investigations of cell signaling pathways, networks, and behavior. Starting from January 2019, CCS is proud to announce its affiliation with the International Cell Death Society. The journal now encourages submissions covering all aspects of cell death, including apoptotic and non-apoptotic mechanisms, cell death in model systems, autophagy, clearance of dying cells, and the immunological and pathological consequences of dying cells in the tissue microenvironment.