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Chemokine Receptor Ccr6 Deficiency Alters Hepatic Inflammatory Cell Recruitment and Promotes Liver Inflammation and Fibrosis
- Source :
- PLoS ONE, Vol 10, Iss 12, p e0145147 (2015), Recercat. Dipósit de la Recerca de Catalunya, instname, PLoS ONE, Dipòsit Digital de la UB, Universidad de Barcelona
- Publication Year :
- 2015
- Publisher :
- Public Library of Science (PLoS), 2015.
-
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.
- Subjects :
- Receptors, CCR6
Chemokine
lcsh:Medicine
Alcoholic hepatitis
chemical and pharmacologic phenomena
Inflammation
C-C chemokine receptor type 6
Liver Cirrhosis, Experimental
Mice
03 medical and health sciences
Liver disease
0302 clinical medicine
Liver Cirrhosis, Alcoholic
Fibrosis
Animals
Medicine
lcsh:Science
030304 developmental biology
Mice, Knockout
Liver injury
0303 health sciences
Multidisciplinary
Hepatology
biology
Carbon Tetrachloride Poisoning
business.industry
Macrophages
Monokines
lcsh:R
hemic and immune systems
medicine.disease
Hepatologia
Quimiocines
3. Good health
CCL20
Liver
Immunology
biology.protein
Th17 Cells
lcsh:Q
030211 gastroenterology & hepatology
Chemical and Drug Induced Liver Injury
Inflammation Mediators
Chemokines
medicine.symptom
business
Research Article
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- PLOS ONE
- Accession number :
- edsair.doi.dedup.....4dad2b88c303cf4531e44a3402c56d38