德国莱布尼茨研究所Chiara Romagnani和Timo Rückert共同合作近期取得重要工作进展，他们研究发现了长效NK细胞记忆的克隆扩增和表观遗传。相关工作2022年10月26日在线发表于《自然—免疫学》杂志上。

研究人员探讨了先天免疫系统内的病原体特异性适应，追踪自然杀伤细胞（NK）对人类巨细胞病毒（HCMV）感染的记忆。利用体外NK细胞的单细胞多组学图谱和体细胞线粒体DNA突变作为内源性条形码，研究人员发现在HCMV⁺个体中适应性NK细胞的大量克隆扩增。NK细胞克隆型的特点是富含AP1基序的趋同炎症记忆特征，叠加在一套克隆特异性的可接近染色质区域上。

随着时间的推移，NK细胞克隆稳定保持特定的表观遗传状态，揭示染色质可及性克隆遗传塑造了表观遗传记忆库。总之，研究人员确定了人类先天性免疫系统中的克隆扩张和持久性，表明这些机制的进化与抗原受体的多样化无关。

据了解，具有体细胞多样化受体的细胞的克隆扩增，及其作为记忆细胞的长期维持是适应性免疫的一个标志。

附：英文原文

Title: Clonal expansion and epigenetic inheritance of long-lasting NK cell memory

Author: Rckert, Timo, Lareau, Caleb A., Mashreghi, Mir-Farzin, Ludwig, Leif S., Romagnani, Chiara

Issue&Volume: 2022-10-26

Abstract: Clonal expansion of cells with somatically diversified receptors and their long-term maintenance as memory cells is a hallmark of adaptive immunity. Here, we studied pathogen-specific adaptation within the innate immune system, tracking natural killer (NK) cell memory to human cytomegalovirus (HCMV) infection. Leveraging single-cell multiomic maps of ex vivo NK cells and somatic mitochondrial DNA mutations as endogenous barcodes, we reveal substantial clonal expansion of adaptive NK cells in HCMV+ individuals. NK cell clonotypes were characterized by a convergent inflammatory memory signature enriched for AP1 motifs superimposed on a private set of clone-specific accessible chromatin regions. NK cell clones were stably maintained in specific epigenetic states over time, revealing that clonal inheritance of chromatin accessibility shapes the epigenetic memory repertoire. Together, we identify clonal expansion and persistence within the human innate immune system, suggesting that these mechanisms have evolved independent of antigen-receptor diversification.

DOI: 10.1038/s41590-022-01327-7

Source: https://www.nature.com/articles/s41590-022-01327-7