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NK细胞的全基因识别形成了中性粒细胞透到心脏全基因移植的重编程

Erik H Koritzinsky^1,2, Karen S Keslar¹, Robert L Fairchild^1,3,2

¹Department of Inflammation and Immunity, Cleveland Clinic Research, Cleveland Clinic Cleveland, OH.

bioRxiv : the preprint server for biology

|November 19, 2025

概括

免疫反应和移植改变了中性粒细胞的可塑性. 一种新型的混合中性粒细胞子集富含全移植是由NK细胞识别驱动的,提供了改善移植结果的标.

科学领域:

免疫学免疫学免疫学
移植生物学移植生物学
细胞异质性细胞异质性

背景情况:

中性粒细胞表现出不同的表型和功能.
组织微环境在感染和癌症中影响中性粒细胞状态.
不同免疫和移植对中性粒细胞可塑性的影响尚不清楚.

研究的目的:

研究非免疫反应和移植器官微环境如何影响中性粒细胞子集的分化和可塑性.
在小鼠心脏移植模型中分析中性粒细胞异质性.

主要方法:

使用了一种小鼠异型心脏移植模型.
采用了高维流细胞计和转录组分析.
比较MHC不匹配的异位移植中的中性粒细胞与异位移植中的异位移植.

主要成果:

中性粒细胞的发育倾向于未成熟的,干扰素刺激基因 (ISG) +子集,无论是异构体接收者还是异构体接收者.
中性粒细胞在所有移植中保持了ISG+表型,但在异位移植中没有.
一个由NK细胞识别驱动的新型IFIT1+ dcTRAIL-R1+杂交中性粒细胞种群被丰富在所有移植中.
由于移植微环境,两种移植类型中的中性粒细胞都采用了成熟的,亲血管的dcTRAIL-R1+表型.

结论:

NK细胞的先天性全基因识别调节了全基因移植中中性粒细胞的可塑性.
在所有移植中确定了一种新的混合中性粒细胞子集.
这些发现使得有针对性的策略能够通过调节中性粒细胞子集来改善固体器官移植结果.

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