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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. Copyright © 2016. Published by Elsevier Inc.


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. NKp80 Defines a Critical Step during Human Natural Killer Cell Development. Cell reports. 2016 Jul 12;16(2):379-391

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PMID: 27373165

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