肺部的T细胞获得许可进入中枢神经系统
Francesca Odoardi1, Christopher Sie, Kristina Streyl
1Institute for Multiple Sclerosis Research, Department of Neuroimmunology, Gemeinnützige Hertie-Stiftung and University Medical Centre Göttingen, 37073 Göttingen, Germany.
Nature
|August 24, 2012
概括
与之前的观点相反,T细胞爆发不会轻易进入中枢神经系统 (CNS). 相反,肺组织的居住重新编程T细胞,使其迁移到中枢神经系统,并导致多发性硬化症等自身免疫性疾病.
科学领域:
- 神经免疫学 神经免疫学
- 自免疫性疾病 自免疫性疾病
- 移动通信贩运 移动通信贩运
背景情况:
- 血脑屏障 (BBB) 通常保护中枢神经系统 (CNS) 免受外围免疫细胞的侵害.
- 在多发性硬化症中,T细胞被认为会破坏BBB以启动中枢神经系统自身免疫.
- 这个模型假设T细胞为随后的免疫细胞进入准备BBB.
研究的目的:
- 为了研究T细胞在实验性自身免疫脑膜炎中进入中枢神经系统的初始进入机制.
- 为了确定T细胞爆发是否需要预先激活BBB才能进入中枢神经系统.
- 探索外周器官,特别是肺在T细胞激活和中枢神经系统迁移中的作用.
主要方法:
- 利用一个路易斯老鼠模型的实验性自身免疫脑膜炎.
- 转移的T细胞爆发静脉和内.
- 分析了T细胞的基因表达特征和迁移模式.
- 研究了肺组织和相关的淋巴体结构在T细胞重编程中的作用.
主要成果:
- 静脉传输的T细胞爆发不能有效地进入中枢神经系统或准备BBB.
- 在肺组织中暂时停留后,T细胞爆发获得了中枢神经系统进入能力.
- 肺部住院诱导了显著的基因表达变化,包括细胞运动和粘附分子的上调,如ninjurin 1.
- 在肺部发现了激活和静止的髓反应T细胞,局部刺激导致扩散和迁移到中枢神经系统.
- 直接转移到呼吸道的T细胞表现出类似的迁移模式,并保留了病原性.
结论:
- 肺部是T细胞激活和重编程的关键位置,促进它们迁移到中枢神经系统.
- T细胞进入中枢神经系统并不取决于初始的BBB制备,而是取决于肺引起的迁移性质.
- 这一发现挑战了中枢神经系统自身免疫启动的传统模型,并突出了肺在协调T细胞介导的自身免疫反应中的作用.
相关概念视频
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