CXC Chemokine Ligand 16 Promotes Integrin-Mediated Adhesion of Liver-Infiltrating Lymphocytes to Cholangiocytes and Hepatocytes within the Inflamed Human Liver

• Published in: The Journal of immunology (1950) 2005-01, Vol.174 (2), p.1055-1062
• Main Authors: Heydtmann, Mathis, Lalor, Patricia F, Eksteen, J. Albertus, Hubscher, Stefan G, Briskin, Mike, Adams, David H
• Format: Article
• Language: English
• Subjects: Cell Adhesion - immunology; Cell Movement - immunology; Cell Separation; Cells, Cultured; Chemokine CXCL16; Chemokines, CXC - biosynthesis; Chemokines, CXC - physiology; Chronic Disease; Endothelium, Vascular - immunology; Endothelium, Vascular - metabolism; Endothelium, Vascular - pathology; Hepatitis C virus; Hepatitis C, Chronic - complications; Hepatocytes - immunology; Humans; Integrin alpha4beta1 - metabolism; Integrins - physiology; Liver - immunology; Liver - pathology; Liver Cirrhosis - immunology; Liver Cirrhosis - pathology; Liver Failure - immunology; Lymphocyte Subsets - immunology; Lymphocyte Subsets - pathology; Membrane Proteins - biosynthesis; Membrane Proteins - physiology; Receptors, Chemokine; Receptors, CXCR6; Receptors, Cytokine - biosynthesis; Receptors, Cytokine - physiology; Receptors, G-Protein-Coupled - biosynthesis; Receptors, G-Protein-Coupled - physiology; Receptors, Immunologic - biosynthesis; Receptors, Immunologic - physiology; Receptors, Scavenger; Receptors, Virus - biosynthesis; Receptors, Virus - physiology; Rheology; Signal Transduction - immunology; Up-Regulation - immunology; Vascular Cell Adhesion Molecule-1 - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.174.2.1055

Lymphocyte recruitment to the liver is critical for viral clearance in acute hepatitis and in the pathogenesis of chronic inflammatory liver disease when persistent chronic inflammation leads to fibrosis and cirrhosis. Chemokines regulate leukocyte recruitment and positioning in tissues and are thus critical regulators of chronic inflammation. The chemokine CXCL16, which is found in liver tissue, exists in a transmembrane as well as soluble form, providing a potential mechanism for localization to particular structures. We studied the role of CXCL16 and its receptor CXCR6 in lymphocyte recruitment and retention in the liver. A higher proportion of CXCR6(+) T cells was detected in blood of hepatitis C virus patients compared with healthy subjects, and in chronic inflammatory liver disease >60% of intrahepatic T cells expressed CXCR6, including CD4, CD8, and CD56(+) T cells compared with