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单细胞空间转录组学揭示了慢性,活跃的抗体介导排斥中的细胞内细胞激活和联体受体关系

Alessia Giarraputo¹, Evelyn Metzger², Nicole Brousaides¹

¹Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

Kidney international

|October 31, 2025

概括

空间转录学揭示了质内皮细胞,NK细胞和巨细胞如何在慢性活性抗体中介排斥 (CAMR) 中相互作用,揭示了移植功能障碍的新分子标.

科学领域:

腎臟病學 (nephrology) 是一種醫學專業.
免疫学免疫学免疫学
分子生物学分子生物学

背景情况:

慢性活性抗体中介排斥 (CAMR) 是晚期移植失败的主要原因.
移植质细胞病变是CAMR的一个标志,涉及质内皮细胞 (GEC),自然杀手细胞 (NK) 和巨细胞.
目前的技术缺乏在CAMR中研究空间分子相互作用的分辨率.

研究的目的:

使用高分辨率空间转录学阐明CAMR的空间分子机制.
在CAMR中识别GEC,NK细胞和巨细胞之间的细胞特异性分子相互作用.

主要方法:

使用CosMx空间分子成像仪用于用CAMR和对照进行脏活检的空间转录学.
应用细胞类型,聚类,差异性基因表达和配体受体分析.
在单细胞分辨率下研究空间近距离和分子相互作用.

主要成果:

鉴定了36种细胞类型和局部GEC亚型,NK细胞,以及质细胞内的巨细胞.
揭示了NK细胞和巨细胞中与细胞毒性和CAMR中的免疫识别相关的上调基因.
在CAMR中发现了独特的GEC转录形状,包括补充保护和IFNγ信号传递的途径.
确定了新的GEC-NK细胞和GEC-巨细胞连接体-受体相互作用 (例如IL33/IL1RL1,HLA-DQA1/FCGR3A),与内皮损伤有关.

结论:

高分辨率的空间转录组学提供了前所未有的洞察力来了解CAMR的病原性.
突出细胞特异激活状态和GEC,NK细胞和巨细胞之间的分子交叉声.
在CAMR中确定了减轻脏全移植功能障碍的潜在治疗标.

关键词:

通过抗体介导的排斥.质内皮质的质内皮.巨细胞是什么?巨细胞是什么?自然杀手细胞是自然杀手细胞.空间转录学空间转录学移植质细胞病变移植质细胞病变

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