title: A human natural killer cell subset provides an innate source of IL-22 for mucosal immunity.
abstract: Natural killer (NK) cells are classically viewed as lymphocytes that provide innate surveillance against virally infected cells and tumour cells through the release of cytolytic mediators and interferon (IFN)-gamma. In humans, blood CD56(dim) NK cells specialize in the lysis of cell targets. In the lymph nodes, CD56(bright) NK cells secrete IFN-gamma cooperating with dendritic cells and T cells in the generation of adaptive responses. Here we report the characterization of a human NK cell subset located in mucosa-associated lymphoid tissues, such as tonsils and Peyer's patches, which is hard-wired to secrete interleukin (IL)-22, IL-26 and leukaemia inhibitory factor. These NK cells, which we refer to as NK-22 cells, are triggered by acute exposure to IL-23. In vitro, NK-22-secreted cytokines stimulate epithelial cells to secrete IL-10, proliferate and express a variety of mitogenic and anti-apoptotic molecules. NK-22 cells are also found in mouse mucosa-associated lymphoid tissues and appear in the small intestine lamina propria during bacterial infection, suggesting that NK-22 cells provide an innate source of IL-22 that may help constrain inflammation and protect mucosal sites.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri 63110, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: Cella
authors.forename: Anja
authors.initials: A
authors.lastname: Fuchs
authors.forename: William
authors.initials: W
authors.lastname: Vermi
authors.forename: Fabio
authors.initials: F
authors.lastname: Facchetti
authors.forename: Karel
authors.initials: K
authors.lastname: Otero
authors.forename: Jochen K M
authors.initials: JK
authors.lastname: Lennerz
authors.forename: Jason M
authors.initials: JM
authors.lastname: Doherty
authors.forename: Jason C
authors.initials: JC
authors.lastname: Mills
authors.forename: Marco
authors.initials: M
authors.lastname: Colonna
mesh_terms: D000818:Animals; D019002:CD56 Antigen / Q000032:analysis; D002448:Cell Adhesion; D054418:Chemokine CCL20 / Q000096:biosynthesis / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology*; D016753:Interleukin-10 / Q000378:metabolism; D053759:Interleukin-23 / Q000276:immunology; D007378:Interleukins / Q000096:biosynthesis* / Q000276:immunology* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D053605:Leukemia Inhibitory Factor / Q000096:biosynthesis; D051379:Mice; D009000:Monocytes / Q000276:immunology; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology; D054399:Receptors, CCR6 / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D051193:Toll-Like Receptors / Q000276:immunology; D000097043:Interleukin-22
chemical_list: D019002:CD56 Antigen; D054418:Chemokine CCL20; D016753:Interleukin-10; D053759:Interleukin-23; D007378:Interleukins; D053605:Leukemia Inhibitory Factor; D054399:Receptors, CCR6; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D051193:Toll-Like Receptors; D000097043:Interleukin-22; C108355:CCL20 protein, human; C106311:CCR6 protein, human; C406767:IL26 protein, human; C507837:LIF protein, human; C494079:STAT1 protein, human; C494086:STAT3 protein, human