在渐进的多发性硬化症中,T淋巴细胞介导的突触细胞再次出现
Krizia Sanna1, Antonio Bruno2,3, Sara Balletta3
1Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
Frontiers in immunology
|June 24, 2024
概括
来自二级渐进性多发性硬化症 (SPMS) 患者的T细胞恶化了神经元刺激能力. 西波尼莫德是一种斯芬戈-1-酸盐受体调节剂,可以逆转这种T细胞诱导的突触毒性,为进展性MS提供潜在的治疗标.
科学领域:
- 神经免疫学 神经免疫学
- 神经药理学神经药理学
- 多发性硬化症的发病因子
背景情况:
- 二次渐进性多发性硬化症 (SPMS) 的特点是,在复发性缓解性多发性硬化症 (RRMS) 过程后,不可逆转的残疾累积.
- 目前的治疗方法缺乏可靠跟踪RRMS到SPMS过渡的工具.
- 来自RRMS患者的T细胞加剧了神经元刺激性传播,这是一个没有缓解的突触毒性事件.
研究的目的:
- 调查T细胞介导的突触毒性在SPMS期间重新出现的假设.
- 在SPMS中探索siponimod的突触保护作用,这是一个sphingosine 1-phosphate受体 (S1PR) 调节器.
主要方法:
- 从健康对照组 (HC),SPMS患者和接受西波尼莫德治疗的SPMS患者收集的数据.
- 用人类T细胞在小鼠皮层-状切片上进行了嵌合体实验,以记录谷氨酸活性.
- 用EAE小鼠T细胞和S1PR调节器进行同源的仿真实验,以确定涉及的特定受体.
主要成果:
- 与HC T细胞相比,来自SPMS患者的T细胞显著增加了状刺激性突触传播.
- 西波尼莫德治疗有效地挽救了SPMS患者衍生的T细胞诱导的突触毒性.
- 同类的模拟实验确定了S1P5R作为Siponomod保护作用中介的受体.
结论:
- 从RRMS过渡到SPMS与T细胞介导的突触毒性再次出现有关.
- 西波尼莫德在抵消T细胞诱导的兴奋毒性方面表现出有效性.
- 炎症性突触症是进展性多发性硬化症的一个重要因素,是有前途的治疗点.
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