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TNFSF14⁺自然杀手细胞通过限制白介导的树叶层细胞衰老来防止自发流产

Jia-Wei Shi^1,2,3, Zhen-Zhen Lai², Wen-Jie Zhou⁴

¹Department of Reproductive Immunology, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, People's Republic of China.

The EMBO journal

|September 11, 2024

概括

与分支链氨基酸 (BCAA) 运输相关的断层 stromal 细胞衰老会影响怀孕. 果性NK细胞通过TNFSF14/TNFRSF14调节这个过程,为复发性自发性流产提供了潜在的治疗方法.

科学领域:

生殖生物学生殖生物学
细胞衰老细胞衰老
免疫学免疫学免疫学

背景情况:

决定性化涉及子宫内膜的转变,用于怀孕.
衰老的果叶 stromal 细胞 (DSCs) 在果叶化过程中积累.
调节DSC衰老的机制尚未完全理解.

研究的目的:

研究分支链氨基酸 (BCAA) 在DSC衰老中的作用.
在调节衰老过程中,阐明树叶自然杀手 (dNK) 细胞和DSC之间的相互作用.
确定自发流产的潜在治疗目标.

主要方法:

在ESC和DSC上的单细胞RNA转录组学.
在体外细胞培养中使用BCAA操纵.
在体内小鼠模型与饮食和遗传修改.
对人类患者样本的分析.

主要成果:

增加的SLC3A2转运体表达与DSC衰老相关.
氨酸枯竭减少了衰老;高氨酸饮食增加了老化和小鼠的胚胎损失.
通过p38 MAPK通路,BCAA诱导了DSC衰老.
通过TNFSF14/TNFRSF14相互作用,dNK细胞抑制了DSC衰老.
NK细胞枯竭或TNFRSF14缺乏导致了不良的妊娠结果.
复发性自发性流产的人类患者表现出过度的子宫衰老,高BCAA摄入量和低TNFRSF14.

结论:

dNK细胞通过TNFSF14/TNFRSF14通路调节DSC衰老平衡.
DSC衰老,BCAA新陈代谢和dNK细胞功能的失调有助于自发流产.
准TNFSF14/TNFRSF14通路可以防止与衰老相关的自发流产.

关键词:

堕胎堕胎堕胎衰老的衰老衰老的衰老决心实现二元化叶氨酸 (Leucine) 是一种蛋白质.这是TNFRSF14

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