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Blood, 23 April 2009, Vol. 113, No. 17, pp. 4008-4010.
Prepublished online as a Blood First Edition Paper on February 24, 2009; DOI 10.1182/blood-2008-12-192443.
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Submitted December 2, 2008
Accepted January 12, 2009
Stage three immature human natural killer cells found in secondary lymphoid tissue constitutively and selectively express the TH17 cytokine interleukin-22
Tiffany Hughes, Brian Becknell, Susan McClory, Edward Briercheck, Aharon G. Freud, Xiaoli Zhang, Hsiaoyin Mao, Gerard Nuovo, Jianhua Yu, and Michael A. Caligiuri*
Integrated Biomedical Graduate Program, The Ohio State University College of Medicine, Columbus, OH, United States
Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, United States
Medical Scientist Program, The Ohio State University College of Medicine, Columbus, OH, United States
The Department of Pathology, Stanford University School of Medicine, Palo Alto, CA, United States
Center for Biostatistics, The Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, OH, United States
The Department of Internal Medicine, The Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, OH, United States
Department of Pathology, Division of Hematology/Oncology, The Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, OH, United States
* Corresponding author; email: michael.caligiuri{at}osumc.edu.
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 three immature (i) human NK cells in SLT constitutively and selectively express IL-22, a TH17 cytokine important for mucosal immunity, while 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- nor possess cytolytic activity. In summary, human stage three iNK cells are highly enriched for IL-22 and IL-26 messenger RNA, IL-22 protein production, but do not express IL-17A or IL-17F.
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