title: Stage 3 immature human natural killer cells found in secondary lymphoid tissue constitutively and selectively express the TH 17 cytokine interleukin-22.
abstract: 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.
authors.affiliation: Integrated Biomedical Graduate Program, The Ohio State University College of Medicine, Columbus, Ohio, USA.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Hughes
authors.forename: Brian
authors.initials: B
authors.lastname: Becknell
authors.forename: Susan
authors.initials: S
authors.lastname: McClory
authors.forename: Edward
authors.initials: E
authors.lastname: Briercheck
authors.forename: Aharon G
authors.initials: AG
authors.lastname: Freud
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhang
authors.forename: Hsiaoyin
authors.initials: H
authors.lastname: Mao
authors.forename: Gerard
authors.initials: G
authors.lastname: Nuovo
authors.forename: Jianhua
authors.initials: J
authors.lastname: Yu
authors.forename: Michael A
authors.initials: MA
authors.lastname: Caligiuri
mesh_terms: D006801:Humans; D020381:Interleukin-17 / Q000276:immunology*; D007378:Interleukins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D038041:Lymphopoiesis / Q000276:immunology*; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D000097043:Interleukin-22
chemical_list: D020381:Interleukin-17; D007378:Interleukins; D012333:RNA, Messenger; D000097043:Interleukin-22