中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (5): 1046-1051.doi: 10.4103/1673-5374.355767

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

浸润中性粒细胞的白细胞介素17A参与创伤性脑损伤诱发的神经炎症

  

  • 出版日期:2023-05-15 发布日期:2022-11-01
  • 基金资助:
    中国国家自然科学基金项目(81771327),中枢神经系统损伤基础科学与临床转化研究平台建设项目(PXM2020_026280_ 000002)

Neutrophil-derived interleukin-17A participates in neuroinflammation induced by traumatic brain injury

Xiao-Jian Xu1, Qian-Qian Ge1, 2, Meng-Shi Yang1, 2, Yuan Zhuang1, 2, Bin Zhang1, 2, Jin-Qian Dong1, 2, Fei Niu1, Hao Li1, 2, Bai-Yun Liu1, 2, 3, 4, *   

  1. 1Beijing Key Laboratory of Central Nervous System Injury, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China;  2Beijing Key Laboratory of Central Nervous System Injury and Department of Neurosurgery, Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Capital Medical University, Beijing, China;  3Nerve Injury and Repair Center of Beijing Institute for Brain Disorders, Beijing, China;  4China National Clinical Research Center for Neurological Diseases, Beijing, China
  • Online:2023-05-15 Published:2022-11-01
  • Contact: Bai-Yun Liu, MD, liubaiyun1212@163.com.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, No. 81771327 (to BYL), and Construction of Central Nervous System Injury Basic Science and Clinical Translational Research Platform, Budget of Beijing Municipal Health Commission 2020, No. PXM2020_026280_000002 (BYL).

摘要:

脑损伤后,中性粒细胞的浸润和异常激活会导致组织损伤和炎症加剧,但连接活化的中性粒细胞与神经炎症的介质尚未完全阐明。为寻找导致创伤性脑损伤后中性粒细胞介导的神经炎症的调节因子,实验以受控皮质冲击模拟构建了创伤性脑损伤小鼠模型。损伤后7d(亚急性期)时,转录组测序发现,模型小鼠脑组织中促炎因子白细胞介素17A相关通路显著上调,提示白细胞介素17A可能参与了神经炎症反应。以双重免疫荧光染色鉴定白细胞介素17A的主要细胞来源,发现白细胞介素17A主要由中性粒细胞而不是神经胶质细胞或神经元分泌。同时实验还发现白细胞介素17A介导的促炎反应的主要效应因子核因子κB和Stat3也在损伤后被激活。这一结果表明,白细胞介素17A参与了创伤性脑损伤亚急性期的中性粒细胞诱发的神经炎症,可能成为创伤性脑损伤的一个潜在的治疗靶点。

https://orcid.org/0000-0001-8204-2623 (Bai-Yun Liu)

关键词: 创伤性脑损伤, 神经炎症, 中性粒细胞, 白细胞介素17A, 免疫浸润, 继发性脑损伤, 神经退行性疾病, 转录组, 先天免疫, 转录因子

Abstract: After brain injury, infiltration and abnormal activation of neutrophils damages brain tissue and worsens inflammation, but the mediators that connect activated neutrophils with neuroinflammation have not yet been fully clarified. To identify regulators of neutrophil-mediated neuroinflammation after traumatic brain injury, a mouse model of traumatic brain injury was established by controlled cortical impact. At 7 days post-injury (sub-acute phase), genome-wide transcriptomic data showed that interleukin 17A-associated signaling pathways were markedly upregulated, suggesting that interleukin 17A may be involved in neuroinflammation. Double immunofluorescence staining showed that interleukin 17A was largely secreted by neutrophils rather than by glial cells and neurons. Furthermore, nuclear factor-kappaB and Stat3, both of which are important effectors in interleukin 17A-mediated proinflammatory responses, were significantly activated. Collectively, our findings suggest that neutrophil-derived interleukin 17A participates in neutrophil-mediated neuroinflammation during the subacute phase of traumatic brain injury. Therefore, interleukin 17A may be a promising therapeutic target for traumatic brain injury.

Key words: immune infiltration, innate immunity, interleukin-17A, neurodegenerative disease, neuroinflammation, neutrophils, secondary brain injury, transcription factor, transcriptome, traumatic brain injury