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胸细胞中年龄相关的Zap70表达调节了新生儿调节性T细胞谱的选择

Brian D Stadinski¹, Elizabeth A Mills², Preston A Humphries²

¹Department of Pathology, University of Massachusetts Chan Medical School, Worcester, MA, USA.

Nature immunology

|October 7, 2025

概括

新生儿胸细胞减少了Zap70,损害了负选择,并允许自我反应调节T (Treg) 细胞发育. 这种依赖年龄的Zap70调节会影响Treg细胞选择和免疫耐受性.

科学领域:

免疫学免疫学免疫学
发育生物学发展生物学
细胞信号传输细胞信号传输

背景情况:

调节性T (Treg) 细胞对于免疫耐受性至关重要.
与成年人相比,新生儿Treg细胞群体表现出更高比例的自我反应克隆.
控制胸腺中依赖年龄的Treg细胞选择的机制尚未完全理解.

研究的目的:

为了研究新生儿和成人Treg细胞之间的胸膜选择中的分子差异.
识别关键信号通路,有助于年龄依赖的Treg细胞谱系偏差.
探索Zap70在调节胸膜发育过程中的负选择中的作用.

主要方法:

来自新生儿和成年小鼠的胸细胞群的比较分析.
在胸膜选择过程中评估Zap70表达和信号动态.
对Zap70表达和LAT信号通路的基因调节.
对ZAP70表达的人类儿科胸膜样本的分析.

主要成果:

新生儿胸细胞在选择过程中表现出明显较低的Zap70上调,与成人胸细胞相比.
减少Zap70导致信号减弱,造成瓶,限制负选择.
较低的Zap70表达允许自我反应克隆逃脱删除,有助于新生儿Treg细胞偏差.
在小鼠中调节Zap70水平改变了自我反应克隆的选择,增强新生儿信号促进了删除.
人类儿科胸膜样本在婴儿中显示ZAP70表达低,与活跃Treg细胞发育期相关.

结论:

年龄依赖的Zap70表达是胸腺中负选择的关键调节者.
新生儿胸细胞中的Zap70依赖信号减弱允许潜在的自我反应Treg细胞克隆的生存.
这些发现提供了对Treg细胞谱系偏差的发育基础和对免疫耐受性的影响的见解.

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