NKG2D Signaling between Human NK Cells Enhances TACE-Mediated TNF-α Release

J Immunol. 2017 Oct 15;199(8):2865-2872. doi: 10.4049/jimmunol.1700647. Epub 2017 Sep 11.

Abstract

NK group 2 member D (NKG2D) is a strong NK cell-activating receptor, with engagement by ligands triggering granule release and cytokine production. The function of NKG2D signaling in NK cells has largely been studied in the context of engagement of the receptor by ligands expressed on the surface of target cells. We report that upon activation with IL-12, IL-15, and IL-18 human NK cells express NKG2D ligands of the UL16 binding protein family on the cell surface. NKG2D-ligand interaction between cytokine-stimulated NK cells increases the activity of the metalloprotease TNF-α-converting enzyme. This enhanced TNF-α-converting enzyme activity significantly increases the release of TNF-α and UL16 binding protein from the surface of the NK cells. These results demonstrate that NKG2D signaling is critical for maximal TNF-α release by NK cells. Further, they demonstrate a role for NKG2D-ligand interaction via homotypic NK cell contact in NK cell effector function.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM17 Protein / genetics
  • ADAM17 Protein / metabolism*
  • Cell Communication
  • Cells, Cultured
  • Cytotoxicity, Immunologic
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism
  • Humans
  • Immunity, Innate
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Interleukin-12 / immunology
  • Interleukin-15 / immunology
  • Interleukin-18 / immunology
  • Killer Cells, Natural / immunology*
  • Lymphocyte Activation
  • NK Cell Lectin-Like Receptor Subfamily K / metabolism*
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • GPI-Linked Proteins
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-15
  • Interleukin-18
  • NK Cell Lectin-Like Receptor Subfamily K
  • Tumor Necrosis Factor-alpha
  • ULBP2 protein, human
  • Interleukin-12
  • ADAM17 Protein
  • ADAM17 protein, human