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

Lucas Rebuffet, Janine E. Melsen, Bertrand Escalière, Daniela Basurto-Lozada, Avinash Bhandoola, Niklas K. Björkström, Yenan T. Bryceson, Roberta Castriconi, Frank Cichocki, Marco Colonna, Daniel M. Davis, Andreas Diefenbach, Yi Ding, Muzlifah Haniffa, Amir Horowitz, Lewis L. Lanier, Karl Johan Malmberg, Jeffrey S. Miller, Lorenzo Moretta, Emilie Narni-MancinelliLuke A.J. O’Neill, Chiara Romagnani, Dylan G. Ryan, Simona Sivori, Dan Sun, Constance Vagne, Eric Vivier

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1474-1488
Number of pages15
JournalNature immunology
Volume25
Issue number8
DOIs
StatePublished - Aug 2024

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© The Author(s) 2024.

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  • Journal Article

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