CXCR3-dependent recruitment and CCR6-mediated positioning of Th-17 cells in the inflamed liver

• DOI: 10.1016/j.jhep.2012.07.008
• Publication Date: 2012-07-14T07:26:45Z
• Authors: Ye Htun Oo; Vanessa Banz; Dean Kavanagh; Evaggelia Liaskou; David R. Withers; Elizabeth Humphreys; Gary M. Reynolds; Laura Lee-Turner; Neena Kalia; Stefan G. Hubscher; Paul Klenerman; Bertus Eksteen; David H. Adams
• Keywords: CCL20; CXCR3; CXCL16

IL-17 secreting CD4 (Th17) and CD8 (Tc17) T cells have been implicated in immune-mediated liver diseases, but the molecular basis for their recruitment positioning within is unknown.The phenotype migratory behaviour of human liver-derived Th17 Tc17 were investigated by flow cytometry chemotaxis flow-based adhesion assays. The murine to was studied vivo using intra-vital microscopy.IL-17(+) comprised 1-3% cell infiltrate inflammatory diseases included both cells. They expressed RORC IL-23 receptor subsets that secreted IL-22 interferon-γ. high levels CXCR3 CCR6, also CXCR6. Binding sinusoidal endothelium from dependent on β1 β2 integrins, CXCR3, and, case cells, VAP-1. via sinusoids mice with inflammation reduced treatment antibodies against ligands, confirming role vivo. In liver, IL-17(+) detected portal infiltrates close inflamed bile ducts expressing CCR6 ligand CCL20. Cytokine-treated cholangiocytes CCL20 induced CCR6-dependent migration suggesting local cholangiocyte chemokine secretion localises ducts.CXCR3 promotes blood into injury. Their subsequent near cholangiocyte-secreted