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天体细胞干扰素-马信号减轻了通过PD-L1慢性中枢神经系统自身免疫期间的炎症

Brandon C Smith^1,2, Rachel A Tinkey^1,3, Orion D Brock^1,4

¹Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue/NC30, Cleveland, OH, 44195, USA.

Journal of neuroinflammation

|October 12, 2023

概括

星球细胞中的干扰素-马信号调节PD-L1,在多发性硬化症模型中减少炎症和疾病严重程度. 这表明PD-1/PD-L1通路向可能有利于患者.

科学领域:

神经免疫学神经免疫学
细胞免疫学细胞免疫学

背景情况:

多发性硬化症 (MS) 涉及中枢神经系统炎症和神经退行.
天体细胞干扰素-玛 (IFNγ) 信号已经显示出神经保护作用,与其典型的炎症功能形成鲜明对比.
免疫检查点PD-1/PD-L1路径与调节免疫反应有关.

研究的目的:

在中枢神经系统 (CNS) 自身免疫的背景下,研究胞IFNγ信号在调节PD-1/PD-L1轴中的作用.
探索针对PD-1/PD-L1途径在实验性自身免疫脑膜炎 (EAE) 中的治疗潜力,这是MS的一个模型.

主要方法:

RNA测序和Ingenuity路径分析IFNγ治疗的天体细胞.
在体外研究评估白细胞亡暴露于IFNγ治疗的星球细胞.
在小鼠体内诱导EAE,有条件的星细胞删除IFNγ受体 (Aldh1l1-CreERT2,Ifngr1fl/fl).
在EAE模型中使用PD-1激动剂.

主要成果:

星球细胞的IFNγ治疗上调调节了编程死亡-连接体1 (PD-L1) 的表达.
在暴露于IFNγ治疗的天体细胞的白细胞中,PD-1/PD-L1对抗作用降低了亡.
对IFNγ受体的有条件的质删除导致PD-L1减少,骨髓细胞透增加,并加剧了EAE.
PD-1激动剂改善了EAE的严重程度,并减少了透到中枢神经系统的白细胞.

结论:

星细胞IFNγ信号通过调节PD-L1.1,减少慢性自身免疫期间的中枢神经系统炎症.
PD-1/PD-L1轴,特别是其在髓状细胞上的表达,在调节中枢神经系统的自身免疫反应方面发挥着至关重要的作用.
针对PD-1/PD-L1通路代表了多发性硬化症的潜在治疗策略.

关键词:

星球细胞是星球细胞.干扰素干扰素干扰素多发性硬化症是多发性硬化症.

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