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单细胞免疫剖析揭示中性粒细胞通过BAFF分泌促进肌痛严重症的恶化
Zhaoxu Zhang1, Jingya Dong2, Mengyuan Qiu1
1Department of Neurology, Peking University People's Hospital, Beijing, 100044, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|September 25, 2025
概括
中性粒细胞通过释放中性粒细胞B细胞激活因子 (BAFF),促进血细胞激活来驱动肌痛性脑膜炎 (MG) 恶化. 针对这一轴可能为MG爆发提供新的治疗方法.
科学领域:
- 免疫学 免疫学 免疫学
- 自免疫性疾病 自免疫性疾病
- 细胞生物学 细胞生物学
背景情况:
- 中性粒细胞涉及到自身免疫性疾病,如肌痛性硬化症 (MG).
- 中性粒细胞在MG恶化中的确切作用尚未完全理解.
- 在MG中潜在的中性细胞B细胞激活因子 (BAFF) - 血细胞轴需要调查.
研究的目的:
- 阐明中性粒细胞在MG恶化中的作用.
- 为了研究中性粒细胞-BAFF-血细胞轴在MG病变的发生.
- 为了确定MG恶化的潜在治疗点.
主要方法:
- 来自MG患者的骨髓和周围血液的单细胞RNA测序 (scRNA-seq).
- 实验性自身免疫性肌痛性肌痛症 (EAMG) 鼠标模型.
- 基因淘汰研究和血清细胞因子分析.
- 对MG患者的临床队列分析.
主要成果:
- 中性粒细胞在MG恶化期间在骨髓中表现出增强的成熟.
- 迁移的中性粒细胞增加BAFF分泌,促进病态B细胞分化和血细胞激活.
- IFN-γ信号通路驱动了过度的BAFF分泌,证实了中性粒细胞-BAFF-血细胞相互作用.
- 具有高中性粒细胞计数的MG患者从telitacicept,BAFF/APRIL抑制剂中获益更多.
结论:
- 中性粒细胞激活与MG恶化有机联系.
- 中性粒细胞-BAFF-血细胞轴在MG病变发生过程中起着重要作用.
- 研究结果表明,在MG中,有可能进行精确向免疫治疗.
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