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感染期间IL-2输送到CD8⁺ T细胞需要MRTF/SRF依赖的基因表达和细胞骨动力学

Diane Maurice^1,2, Patrick Costello¹, Jessica Diring¹

¹Signalling and transcription Laboratory, Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.

Nature communications

|September 11, 2024

概括

血清反应因子 (SRF) 和它的辅因子MRTF-A/B对于感染期间的CD8+T细胞扩张和记忆细胞持久性至关重要. 这条通路调节细胞骨动力学和动因基因表达,对IL-2信号传递和T细胞聚类至关重要.

科学领域:

免疫学免疫学免疫学
分子生物学分子生物学
细胞生物学细胞生物学

背景情况:

对于CD8+ T细胞对病毒感染的反应来说,对内介质双流素-2 (IL-2) 信号传递至关重要.
控制CD8+T细胞IL-2信号传递的精确分子机制尚不完全理解.

研究的目的:

研究转录因子SRF及其辅因子MRTF-A/B在感染期间CD8+T细胞反应中的作用.
阐明将SRF介导的细胞骨调节与IL-2信号传递和T细胞功能联系起来的分子事件.

主要方法:

使用了对Listeria monocytogenes感染的小鼠模型.
生成的Mrtfab-null CD8+ T细胞来评估SRF通路的功能.
分析了T细胞的增殖,分化,同型聚类和基因表达 in vitro 和 in vivo.
研究了F-actin组合和IL-2保留在T细胞聚类中的作用.

主要成果:

与MRTF-A/B一起作用的SRF对于持续的依赖IL-2的CD8+T细胞扩张和记忆细胞持久性至关重要.
Mrtfab-null CD8+ T 细胞表现出同型聚类受损以及细胞骨基因的缺陷表达,包括行动素.
激活诱导的细胞聚类需要F-actin组合,这在Mrtfab-null细胞中受损,导致IL-2保留减少.

结论:

SRF-MRTF信号控制细胞骨动力学和CD8+ T细胞中的actin基因表达.
这一途径对于有效的IL-2信号传递,T细胞聚类以及在感染期间持续的效应/记忆CD8+T细胞反应至关重要.

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