Intravascular Immune Surveillance by CXCR6+ NKT Cells Patrolling Liver Sinusoids

By F. Geissmann, T. Cameron, S. Sidobre, Natasha Manlongat, M. Kronenberg, M. Briskin, Michael Loran Dustin, Dan R. Littman. PLoS Biology, 2005

660 citations recorded by the source corpus.

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 μm/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.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/df7e591cc1435f8c1065c726b17b137d8227f5e0

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In Immunology

1. S. Formenti
2. S. Demaria
3. D. Godfrey
4. J. Zindel
5. P. Kubes
6. C. Auffray
7. A. Bendelac
8. F. Geissmann

Citations in the corpus

• The biology of NKT cells. (2007, background): “CD1d expression in the liver is not required, however, for NKT cell homing (86), and neither is CXCR6 expression by NKT cells, although CXCR6/CXCL16 interactions are essential for survival in this organ (30).”
• Radiation-induced CXCL16 release by breast cancer cells attracts effector T cells (2008, background): “CXCL16 is known to be expressed by dendritic cells, macrophages, and some endothelia and to be up-regulated during inflammation in different tissues and organs (13, 14, 35, 42).”
• The transcription factor PLZF (Zbtb16) directs the effector program of the NKT cell lineage (2008, background): “Peripheral NKT cells preferentially reside in the liver, continuously crawling along the sinusoidal endothelial cells (Geissmann et al., 2005; Godfrey and Berzins, 2007), but they are also present in the spleen, lymph nodes, bone marrow, lung, and gut.”
• Nr4a1-Dependent Ly6Clow Monocytes Monitor Endothelial Cells and Orchestrate Their Disposal (2013, background): “However, the accumulation of crawling leucocytes inside blood vessels may not always lead to extravasation (Geissmann et al., 2005; Devi et al., 2013).”
• International Union of Basic and Clinical Pharmacology. LXXXIX. Update on the Extended Family of Chemokine Receptors and Introducing a New Nomenclature for Atypical Chemokine Receptors (2014, neutral): “, 2002) NKT cells and is important for survival and activation of liver NKT cells in mice (Geissmann et al., 2005; Germanov et al., 2008).”
• Leukocyte migration into inflamed tissues. (2014, background): “Abortive emigration of leukocytes to blood vessels is observed in other settings including natural killer (NK) and NKT cell crawling inside liver sinusoids (Geissmann et al., 2005) and retention of immature B cells in the bonemarrow vasculature (Pereira et al.”
• Raising the NKT cell family (2010, background): “For example, liver NKT cell numbers depend on the chemokine receptor CXCR6 (refs”
• DAMPs, PAMPs, and LAMPs in Immunity and Sterile Inflammation. (2020, background): “Depending on whether an iNKT cell is activated by a foreign or self-antigen, it rapidly secretes the proinflammatory type 1 cytokine interferon (IFN)-γ during infection or secretes type 2 cytokines, such as IL-4 and IL-10, during tissue repair (95, 96).”
• T cell– and B cell–independent adaptive immunity mediated by natural killer cells (2006, background): “Notably, a unique function for the CXCL16-CXCR6 pathway in the retention and survival of NKT cells in the liver has been demonstrate”