2024年7月2日出版的《自然-免疫学》杂志发表了法国国立马赛吕米尼免疫中心Eric Vivier课题组的最新研究成果。他们对人自然杀伤细胞（NK）异质性进行了高维单细胞分析。

研究人员利用单细胞RNA测序（scRNA-seq）和转录组与表位细胞索引测序（CITE-seq）来剖析NK细胞异质性。研究在健康人的血液中发现了三个独特的NK细胞亚群：NK1、NK2和NK3，并进一步将其分为六个不同的亚群。研究人员描述了每个亚群的分子特征、关键转录因子、生物功能、代谢特征和细胞因子反应。研究数据表明，NK细胞有两个不同的本体起源，导致不同的转录轨迹。

此外，研究还分析了NK细胞亚群在肺部、扁桃体和上皮内淋巴细胞中的分布情况，这些亚群分别从健康人和22种肿瘤中分离而来。这种标准化分类有利于促进未来研究的清晰性和一致性，并改善交叉研究比较。

据了解，自然杀伤细胞是先天性淋巴细胞（ILC），有助于对微生物和肿瘤产生免疫反应。它们的分类主要依赖于有限的表面蛋白标记。

附：英文原文

Title: High-dimensional single-cell analysis of human natural killer cell heterogeneity

Author: Rebuffet, Lucas, Melsen, Janine E., Escalire, Bertrand, Basurto-Lozada, Daniela, Bhandoola, Avinash, Bjrkstrm, Niklas K., Bryceson, Yenan T., Castriconi, Roberta, Cichocki, Frank, Colonna, Marco, Davis, Daniel M., Diefenbach, Andreas, Ding, Yi, Haniffa, Muzlifah, Horowitz, Amir, Lanier, Lewis L., Malmberg, Karl-Johan, Miller, Jeffrey S., Moretta, Lorenzo, Narni-Mancinelli, Emilie, ONeill, Luke A. J., Romagnani, Chiara, Ryan, Dylan G., Sivori, Simona, Sun, Dan, Vagne, Constance, Vivier, Eric

Issue&Volume: 2024-07-02

Abstract: Natural killer (NK) cells are innate lymphoid cells (ILCs) contributing to immune responses to microbes and tumors. Historically, their classification hinged on a limited array of surface protein markers. Here, we used single-cell RNA sequencing (scRNA-seq) and cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) to dissect the heterogeneity of NK cells. We identified three prominent NK cell subsets in healthy human blood: NK1, NK2 and NK3, further differentiated into six distinct subgroups. Our findings delineate the molecular characteristics, key transcription factors, biological functions, metabolic traits and cytokine responses of each subgroup. These data also suggest two separate ontogenetic origins for NK cells, leading to divergent transcriptional trajectories. Furthermore, we analyzed the distribution of NK cell subsets in the lung, tonsils and intraepithelial lymphocytes isolated from healthy individuals and in 22 tumor types. This standardized terminology aims at fostering clarity and consistency in future research, thereby improving cross-study comparisons.

DOI: 10.1038/s41590-024-01883-0

Source: https://www.nature.com/articles/s41590-024-01883-0