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HDL结合的基基-1-酸盐抑制了淋巴发育和神经炎症

Victoria A Blaho¹, Sylvain Galvani², Eric Engelbrecht²

¹1] Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, New York 10065, USA [2] Brain and Mind Research Institute, Weill Medical College of Cornell University, New York, New York 10065, USA.

|June 9, 2015

概括

阿波利波蛋白M-sphingosine-1-phosphate (ApoM-S1P) 复合体通过激活原生细胞上的S1P1受体来抑制免疫细胞的产生. 这一发现揭示了一种控制适应性免疫和潜在治疗点的新机制.

科学领域:

免疫学免疫学免疫学
脂质代谢脂质代谢是什么
细胞生物学细胞生物学

背景情况:

脂质调解剂显著影响免疫系统功能.
斯芬哥辛-1-酸盐 (S1P) 调节淋巴细胞的退出,大多数血S1P与HDL颗粒中的阿波利波蛋白M (ApoM) 结合.
ApoM-S1P复合物的特定免疫作用在很大程度上仍未被描述.

研究的目的:

为了研究ApoM-S1P复合物的免疫功能.
阐明ApoM-S1P在调节淋巴细胞发育和免疫反应中的作用.

主要方法:

利用ApoM缺乏 (Apom(-/-)) 的小鼠来研究淋巴发育和免疫反应.
雇佣了S1P1受体的药理激活和遗传过度表达.
在体外和体内评估了造血原生细胞 (LSK) 和常见淋巴原生细胞 (CLP) 的增殖.
在阿波姆小鼠中分析了实验性自身免疫脑膜炎 (EAE) 严重程度.

主要成果:

ApoM-S1P缺乏导致骨髓中LSK和CLP的扩散增加.
在骨髓原始体上S1P1受体的激活抑制了LSK和CLP的扩散.
与阿波M结合的S1P不同,与与专结合的S1P不同,在体外抑制了淋巴结合.
Apom(-/-) 小鼠表现出恶化的EAE与增加的神经炎症和血脑屏障破坏.

结论:

ApoM-S1P-S1P1信号轴对于抑制淋巴细胞区和自适应性免疫反应至关重要.
ApoM-S1P对于淋巴细胞贩运是不可或缺的,但对于通过S1P1激活原始细胞来调节淋巴细胞形成至关重要.
特定的S1P陪伴者具有独特的生物功能,可能为免疫调节提供新的治疗途径.

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