A Human Natural Killer Cell Subset Provides an Innate Source of IL-22 for Mucosal Immunity

Nature. 2009 Feb 5;457(7230):722-5. doi: 10.1038/nature07537. Epub 2008 Nov 2.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CD56 Antigen / analysis
  • Cell Adhesion
  • Chemokine CCL20 / biosynthesis
  • Chemokine CCL20 / metabolism
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism
  • Humans
  • Immunity, Mucosal / immunology*
  • Interleukin-10 / metabolism
  • Interleukin-23 / immunology
  • Interleukins / biosynthesis*
  • Interleukins / immunology*
  • Interleukins / metabolism
  • Killer Cells, Natural / cytology*
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Leukemia Inhibitory Factor / biosynthesis
  • Mice
  • Monocytes / immunology
  • Palatine Tonsil / cytology
  • Palatine Tonsil / immunology
  • Receptors, CCR6 / metabolism
  • STAT1 Transcription Factor / metabolism
  • STAT3 Transcription Factor / metabolism
  • Toll-Like Receptors / immunology

Substances

  • CCL20 protein, human
  • CCR6 protein, human
  • CD56 Antigen
  • Chemokine CCL20
  • IL26 protein, human
  • Interleukin-23
  • Interleukins
  • LIF protein, human
  • Leukemia Inhibitory Factor
  • Receptors, CCR6
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Toll-Like Receptors
  • Interleukin-10
  • interleukin-22