Gut microbiota regulates NKG2D ligand expression on intestinal epithelial cells

Authors

  • Camilla H. F. Hansen,

    Corresponding author
    1. Section of Biomedicine, Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark
    • Full correspondence: Dr. Camilla H. F. Hansen, Section of Biomedicine, Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Thorvaldsensvej 57, 1870 Frederiksberg C, Denmark

      Fax: +45-35332755

      e-mail: camfriis@sund.ku.dk

      Additional correspondence: Dr. Søren Skov, Section of Biomedicine, Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Thorvaldsensvej 57, 1870 Frederiksberg C, Denmark.

      Fax: +45-35332755

      e-mail: sosk@sund.ku.dk

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  • Thomas L. Holm,

    1. Department of Immunopharmacology, Novo Nordisk A/S, Måløv, Denmark
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  • Łukasz Krych,

    1. Department of Food Science, Faculty of Science, University of Copenhagen, Frederiksberg C, Denmark
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  • Lars Andresen,

    1. Section of Biomedicine, Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark
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  • Dennis S. Nielsen,

    1. Department of Food Science, Faculty of Science, University of Copenhagen, Frederiksberg C, Denmark
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  • Ida Rune,

    1. Section of Biomedicine, Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark
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  • Axel K. Hansen,

    1. Section of Biomedicine, Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark
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  • Søren Skov

    Corresponding author
    1. Section of Biomedicine, Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark
    • Full correspondence: Dr. Camilla H. F. Hansen, Section of Biomedicine, Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Thorvaldsensvej 57, 1870 Frederiksberg C, Denmark

      Fax: +45-35332755

      e-mail: camfriis@sund.ku.dk

      Additional correspondence: Dr. Søren Skov, Section of Biomedicine, Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Thorvaldsensvej 57, 1870 Frederiksberg C, Denmark.

      Fax: +45-35332755

      e-mail: sosk@sund.ku.dk

    Search for more papers by this author

Abstract

Intestinal epithelial cells (IECs) are one of a few cell types in the body with constitutive surface expression of natural killer group 2 member D (NKG2D) ligands, although the magnitude of ligand expression by IECs varies. Here, we investigated whether the gut microbiota regulates the NKG2D ligand expression on small IECs. Germ-free and ampicillin-treated mice were shown to have a significant increase in NKG2D ligand expression. Interestingly, vancomycin treatment, which propagated the bacterium Akkermansia muciniphila and reduced the level of IFN-γ and IL-15 in the intestine, decreased the NKG2D ligand expression on IECs. In addition, a similar increase in A. muciniphila and a decreased NKG2D ligand expression was seen after feeding with dietary xylooligosaccharides. A pronounced increase in NKG2D ligand expression was furthermore observed in IL-10-deficient mice. In summary, our results suggest that the constitutive levels of NKG2D ligand expression on IECs are regulated by microbial signaling in the gut and further disfavor the intuitive notion that IEC NKG2D ligand expression is caused by low-grade immune reaction against commensal bacteria. It is more likely that constitutively high IEC NKG2D ligand expression is kept in check by an intestinal regulatory immune milieu induced by members of the gut microbiota, for example A. muciniphila.

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