在激活的T细胞中持续的mTORC1激活会损害老年人对疫苗的反应
Xiaorong Lin1, Yanhua Du2, Shuo Kan1
1Multiscale Research Institute for Complex Systems, Fudan University, Shanghai, China.
Science advances
|April 18, 2025
概括
T细胞衰老会影响疫苗的有效性. 较低的初始T细胞数量通过增加mTORC1活性来降低疫苗接种后的毛囊辅助T细胞 (TFH),但饮食中的白限制可以减轻这种损失.
科学领域:
- 免疫学 免疫学 免疫学
- 衰老研究研究 衰老研究
- 分子生物学分子生物学
背景情况:
- 在老年人中,T细胞衰老与疫苗有效性降低有关.
- 这种与年龄相关的衰退背后的精确分子机制尚未完全理解.
研究的目的:
- 调查初始的原始CD4+T细胞密度在衰老过程中T毛囊辅助 (TFH) 细胞命运中的作用.
- 阐明连接细胞密度,T细胞衰老和疫苗反应的分子途径.
主要方法:
- 在免疫接种后的年轻和老年小鼠中研究了原始的CD4+T细胞密度和TFH细胞分化.
- 研究了哺乳动物目标的拉巴胺素复合物1 (mTORC1) 信号传递和YAP依赖调节的作用.
- 评估了氨酸受限饮食对TFH细胞动态和老年小鼠幽默免疫力的影响.
主要成果:
- 较低的初始原始CD4+T细胞密度与年龄并没有影响峰值TFH分化,但在收缩过程中增加了TFH细胞损失.
- 细胞密度下降导致mTORC1活动持续,影响CXCR5表达和TFH维持.
- 在YAP调节的SLC7A5中介细胞密度对mTORC1和TFH损失的影响.
- 在老老鼠中,氨酸的限制减少了TFH损失,并改善了抗体反应.
结论:
- 最初的T细胞密度对于接种疫苗后的TFH细胞维持至关重要,与年龄相关的下降会影响疫苗的疗效.
- 由于细胞密度较低,mTORC1活动的持续是驱动TFH衰老损失的关键机制.
- 针对mTORC1信号,可能通过饮食干预,提供了一种提高老年人疫苗反应的策略.
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