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Blood. 2009 Apr 23;113(17):4008-10. doi: 10.1182/blood-2008-12-192443. Epub 2009 Feb 24.

Stage 3 immature human natural killer cells found in secondary lymphoid tissue constitutively and selectively express the TH 17 cytokine interleukin-22.

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  • 1Integrated Biomedical Graduate Program, The Ohio State University College of Medicine, Columbus, Ohio, USA.


Considerable functional heterogeneity within human natural killer (NK) cells has been revealed through the characterization of distinct NK-cell subsets. Accordingly, a small subset of CD56(+)NKp44(+)NK cells, termed NK-22 cells, was recently described within secondary lymphoid tissue (SLT) as IL-22(-) when resting, with a minor fraction of this population becoming IL-22(+) when activated. Here we discover that the vast majority of stage 3 immature NK (iNK) cells in SLT constitutively and selectively express IL-22, a T(H)17 cytokine important for mucosal immunity, whereas earlier and later stages of NK developmental intermediates do not express IL-22. These iNK cells have a surface phenotype of CD34(-)CD117(+)CD161(+)CD94(-), largely lack expression of NKp44 and CD56, and do not produce IFN-gamma or possess cytolytic activity. In summary, stage 3 iNK cells are highly enriched for IL-22 and IL-26 messenger RNA, and IL-22 protein production, but do not express IL-17A or IL-17F.

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