Intravascular immune surveillance by CXCR6+ NKT cells patrolling liver sinusoids.
We examined the in vivo behavior of liver natural killer T cells (NKT cells) by intravital fluorescence microscopic imaging of mice in which a green fluorescent protein cDNA was used to replace the gene encoding the chemokine receptor CXCR6. NKT cells, which account for most CXCR6(+) cells in liver, were found to crawl within hepatic sinusoids at 10-20 microm/min and to stop upon T cell antigen receptor activation. CXCR6-deficient mice exhibited a selective and severe reduction of CD1d-reactive NKT cells in the liver and decreased susceptibility to T-cell-dependent hepatitis. CXCL16, the cell surface ligand for CXCR6, is expressed on sinusoidal endothelial cells, and CXCR6 deficiency resulted in reduced survival, but not in altered speed or pattern of patrolling of NKT cells. Thus, NKT cells patrol liver sinusoids to provide intravascular immune surveillance, and CXCR6 contributes to liver-based immune responses by regulating their abundance.
Geissmann
Frederic
F
Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, USA.
Cameron
Thomas O
TO
Sidobre
Stephane
S
Manlongat
Natasha
N
Kronenberg
Mitchell
M
Briskin
Michael J
MJ
Dustin
Michael L
ML
Littman
Dan R
DR
D000818:Animals; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6; D019743:Chemokines, CXC / Q000235:genetics; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology*; D008099:Liver / Q000201:enzymology*; D051379:Mice; D008822:Mice, Transgenic; D054387:Receptors, CXCR; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine / Q000235:genetics / Q000276:immunology*; D051116:Receptors, Scavenger / Q000235:genetics
D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6; D019743:Chemokines, CXC; C498926:Cxcl16 protein, mouse; C482906:Cxcr6 protein, mouse; D054387:Receptors, CXCR; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine; D051116:Receptors, Scavenger; D049452:Green Fluorescent Proteins