Key features and homing properties of NK cells in the liver are shaped by activated iNKT cells

Sci Rep. 2019 Nov 8;9(1):16362. doi: 10.1038/s41598-019-52666-9.

Abstract

The contribution of natural killer (NK) cells to the clearance of hepatic viral infections is well recognized. The recently discovered heterogeneity of NK cell populations renders them interesting targets for immune interventions. Invariant natural killer T (iNKT) cells represent a key interaction partner for hepatic NK cells. The present study addressed whether characteristics of NK cells in the liver can be shaped by targeting iNKT cells. For this, the CD1d-binding pegylated glycolipid αGalCerMPEG was assessed for its ability to modulate the features of NK cells permanently or transiently residing in the liver. In vivo administration resulted in enhanced functionality of educated and highly differentiated CD27+ Mac-1+ NK cells accompanied by an increased proliferation. Improved liver homing was supported by serum-derived and cellular factors. Reduced viral loads in a mCMV infection model confirmed the beneficial effect of NK cells located in the liver upon stimulation with αGalCerMPEG. Thus, targeting iNKT cell-mediated NK cell activation in the liver represents a promising approach for the establishment of liver-directed immune interventions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD1d / metabolism
  • Cell Movement
  • Cell Proliferation
  • Cytomegalovirus / drug effects
  • Cytomegalovirus / immunology*
  • Cytomegalovirus Infections / drug therapy
  • Cytomegalovirus Infections / immunology*
  • Cytomegalovirus Infections / virology
  • Galactosylceramides / pharmacology
  • Glycolipids / pharmacology
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Liver / drug effects
  • Liver / immunology*
  • Liver / metabolism
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Natural Killer T-Cells / drug effects
  • Natural Killer T-Cells / immunology*
  • Natural Killer T-Cells / metabolism
  • Polyethylene Glycols / chemistry

Substances

  • Antigens, CD1d
  • CD1d antigen, mouse
  • Galactosylceramides
  • Glycolipids
  • Polyethylene Glycols