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纯能受体P2RX7指导长寿记忆CD8+T细胞的代谢适应性

Henrique Borges da Silva^1,2, Lalit K Beura^1,3, Haiguang Wang^1,2

¹Center for Immunology, University of Minnesota, Minneapolis, MN, USA.

|July 6, 2018

概括

细胞外ATP (eATP) 表示危险并激活P2RX7受体. 这种受体对长期存活的CD8+T细胞的发展和维持至关重要,对于适应性免疫和疫苗至关重要.

科学领域:

免疫学
细胞生物学
神经科学

背景情况:

细胞外ATP (eATP) 作为危险信号,通过P2RX7激活先天免疫和疼痛通路.
对于eATP和P2RX7在免疫记忆中的作用,特别是适应性免疫,至今还没有得到充分的研究.

研究的目的:

研究纯能受体P2RX7在CD8+T细胞记忆的产生和维持中的作用.
阐明P2RX7影响T细胞分化和功能的机制.

主要方法:

使用小鼠模型评估CD8+T细胞记忆群.
用小鼠和人类CD8+T细胞进行体外研究,以检查代谢和分化效应.
在体内研究P2RX7抑制对神经病痛和T细胞记忆的影响.

主要成果:

P2RX7对于长寿的中央和组织内存CD8+ T细胞的建立,维护和功能装备至关重要.
部分通过AMP激活的蛋白激酶影响 mitochondrial homeostasis 和分化记忆CD8+ T细胞的代谢功能.
在体内P2RX7阻断降低了神经病痛,但也影响了CD8+ T细胞的记忆产生.

结论:

通过eATP激活P2RX7在提醒神经系统和免疫系统对组织损伤方面发挥着双重作用.
P2RX7通路对于持久,功能性的CD8+ T细胞记忆群体的代谢适应性和生存至关重要.
针对P2RX7提供了一种潜在的疼痛管理策略,同时影响适应性免疫力.

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