NKp80 Defines a Critical Step during Human Natural Killer Cell Development

Publication date: Available online 30 June 2016
Source:Cell Reports
Author(s): Aharon G. Freud, Karen A. Keller, Steven D. Scoville, Bethany L. Mundy-Bosse, Stephanie Cheng, Youssef Youssef, Tiffany Hughes, Xiaoli Zhang, Xiaokui Mo, Pierluigi Porcu, Robert A. Baiocchi, Jianhua Yu, William E. Carson, Michael A. Caligiuri
Human natural killer (NK) cells develop in secondary lymphoid tissues (SLTs) through distinct stages. We identified two SLT lineage (Lin)⁻CD34⁻CD117^+/−CD94⁺CD16⁻ “stage 4” subsets according to expression of the C-type lectin-like surface-activating receptor, NKp80: NKp80⁻ (stage “4a”) and NKp80⁺ (stage “4b”). Whereas stage 4b cells expressed more of the transcription factors T-BET and EOMES, produced interferon-gamma, and were cytotoxic, stage 4a cells expressed more of the transcription factors RORγt and AHR and produced interleukin-22, similar to SLT Lin⁻CD34⁻CD117⁺CD94⁻CD16⁻ “stage 3” cells, whose phenotype overlaps with that of group 3 innate lymphoid cells (ILC3s). Co-culture with dendritic cells or transplantation into immunodeficient mice produced mature NK cells from stage 3 and stage 4a populations. These data identify NKp80 as a marker of NK cell maturity in SLTs and support a model of human NK cell development through a stage 4a intermediate with ILC3-associated features.

Graphical abstract

Teaser

Human natural killer (NK) cells have potent effector functions against cancer; how NK cells develop in humans is unclear. Freud et al. demonstrate that NKp80 expression marks functionally mature NK cells as they develop in secondary lymphoid tissues. These findings help define the pathway of human NK cell development.


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