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Intravascular immune surveillance by CXCR6+ NKT cells patrolling liver sinusoids

Frederic Geissmann1, Thomas O Cameron, Stephane Sidobre

  • 1Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, USA.

Plos Biology
|April 1, 2005
PubMed

Insights

Liver natural killer T cells (NKT cells) patrol the liver's sinusoids. The chemokine receptor CXCR6 is crucial for their abundance and function in liver immunity.

Area of Science:

  • Immunology
  • Cell Biology
  • Microscopy

Background:

  • Natural killer T (NKT) cells are crucial immune cells residing in the liver.
  • Their precise behavior and regulation within the hepatic microenvironment remain incompletely understood.
  • The chemokine receptor CXCR6 is highly expressed on liver NKT cells, suggesting a role in their function.

Purpose of the Study:

  • To investigate the in vivo behavior of liver NKT cells using intravital fluorescence microscopic imaging.
  • To determine the role of the chemokine receptor CXCR6 in NKT cell trafficking, function, and immune surveillance within the liver.

Main Methods:

  • Intravital fluorescence microscopic imaging in mice with green fluorescent protein (GFP)-tagged NKT cells.
  • Genetic manipulation to create CXCR6-deficient mice.
  • Analysis of NKT cell behavior, including crawling speed and response to activation.
  • Assessment of liver NKT cell populations and susceptibility to T-cell-dependent hepatitis.

Main Results:

  • Liver NKT cells were observed to crawl within hepatic sinusoids at 10-20 microm/min and arrest upon T cell receptor activation.
  • CXCR6-deficient mice showed a significant reduction in CD1d-reactive NKT cells in the liver.
  • CXCR6 deficiency led to decreased susceptibility to T-cell-dependent hepatitis.
  • The ligand for CXCR6, CXCL16, is expressed on sinusoidal endothelial cells, and its absence reduced NKT cell survival but not patrolling dynamics.

Conclusions:

  • NKT cells perform intravascular immune surveillance by patrolling liver sinusoids.
  • CXCR6 plays a critical role in regulating the abundance of liver NKT cells.
  • CXCR6 signaling contributes significantly to liver-based immune responses and hepatitis pathogenesis.

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