title: Chemokine Receptor Ccr6 Deficiency Alters Hepatic Inflammatory Cell Recruitment and Promotes Liver Inflammation and Fibrosis.
abstract: Chronic liver diseases are characterized by a sustained inflammatory response in which chemokines and chemokine-receptors orchestrate inflammatory cell recruitment. In this study we investigated the role of the chemokine receptor CCR6 in acute and chronic liver injury. In the absence of liver injury Ccr6-/- mice presented a higher number of hepatic macrophages and increased expression of pro-inflammatory cytokines and M1 markers Tnf-α, Il6 and Mcp1. Inflammation and cell recruitment were increased after carbon tetrachloride-induced acute liver injury in Ccr6-/- mice. Moreover, chronic liver injury by carbon tetrachloride in Ccr6-/- mice was associated with enhanced inflammation and fibrosis, altered macrophage recruitment, enhanced CD4+ cells and a reduction in Th17 (CD4+IL17+) and mature dendritic (MHCII+CD11c+) cells recruitment. Clodronate depletion of macrophages in Ccr6-/- mice resulted in a reduction of hepatic pro-inflammatory and pro-fibrogenic markers in the absence and after liver injury. Finally, increased CCR6 hepatic expression in patients with alcoholic hepatitis was found to correlate with liver expression of CCL20 and severity of liver disease. In conclusion, CCR6 deficiency affects hepatic inflammatory cell recruitment resulting in the promotion of hepatic inflammation and fibrosis.
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Affò
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Rodrigo-Torres
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Delia
authors.initials: D
authors.lastname: Blaya
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Oriol
authors.initials: O
authors.lastname: Morales-Ibanez
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Coll
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Millán
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.|Vall d'Hebrón Institut de Recerca (VHIR), Barcelona, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Altamirano
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.|Liver Unit, Hospital Clínic, Faculty of Medicine, University of Barcelona, Barcelona, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Arroyo
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.|Liver Unit, Hospital Clínic, Faculty of Medicine, University of Barcelona, Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Caballería
authors.affiliation: Division of Gastroenterology and Hepatology, Departments of Medicine and Nutrition, University of North Carolina, Chapel Hill, North Carolina, United States of America.
authors.forename: Ramón
authors.initials: R
authors.lastname: Bataller
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.|Liver Unit, Hospital Clínic, Faculty of Medicine, University of Barcelona, Barcelona, Spain.
authors.forename: Pere
authors.initials: P
authors.lastname: Ginès
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
authors.forename: Pau
authors.initials: P
authors.lastname: Sancho-Bru
mesh_terms: D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000235:genetics / Q000276:immunology / Q000473:pathology; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D018836:Inflammation Mediators / Q000276:immunology; D008099:Liver / Q000276:immunology* / Q000473:pathology; D008104:Liver Cirrhosis, Alcoholic / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D015846:Monokines / Q000235:genetics / Q000276:immunology; D054399:Receptors, CCR6 / Q000172:deficiency* / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology
chemical_list: C498126:CCR6 protein, mouse; D018836:Inflammation Mediators; D015846:Monokines; D054399:Receptors, CCR6