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http://purl.uniprot.org/citations/23959575http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/23959575http://www.w3.org/2000/01/rdf-schema#comment"

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Chronic liver injury promotes hepatic inflammation, representing a prerequisite for organ fibrosis. We hypothesized a contribution of chemokine receptor CCR6 and its ligand, CCL20, which may regulate migration of T-helper (Th)17, regulatory, and gamma-delta (γδ) T cells. CCR6 and CCL20 expression was intrahepatically up-regulated in patients with chronic liver diseases (n = 50), compared to control liver (n = 5). Immunohistochemistry revealed the periportal accumulation of CCR6(+) mononuclear cells and CCL20 induction by hepatic parenchymal cells in liver disease patients. Similarly, in murine livers, CCR6 was expressed by macrophages, CD4 and γδ T-cells, and up-regulated in fibrosis, whereas primary hepatocytes induced CCL20 upon experimental injury. In two murine models of chronic liver injury (CCl4 and methionine-choline-deficient diet), Ccr6(-/-) mice developed more severe fibrosis with strongly enhanced hepatic immune cell infiltration, compared to wild-type (WT) mice. Although CCR6 did not affect hepatic Th-cell subtype composition, CCR6 was explicitly required by the subset of interleukin (IL)-17- and IL-22-expressing γδ T cells for accumulation in injured liver. The adoptive transfer of WT γδ, but not CD4 T cells, into Ccr6(-/-) mice reduced hepatic inflammation and fibrosis in chronic injury to WT level. The anti-inflammatory function of hepatic γδ T cells was independent of IL-17, as evidenced by transfer of Il-17(-/-) cells. Instead, hepatic γδ T cells colocalized with hepatic stellate cells (HSCs) in vivo and promoted apoptosis of primary murine HSCs in a cell-cell contact-dependent manner, involving Fas-ligand (CD95L). Consistent with γδ T-cell-induced HSC apoptosis, activated myofibroblasts were more frequent in fibrotic livers of Ccr6(-/-) than in WT mice.

Conclusion

γδ T cells are recruited to the liver by CCR6 upon chronic injury and protect the liver from excessive inflammation and fibrosis by inhibiting HSCs."xsd:string
http://purl.uniprot.org/citations/23959575http://purl.org/dc/terms/identifier"doi:10.1002/hep.26697"xsd:string
http://purl.uniprot.org/citations/23959575http://purl.uniprot.org/core/author"Huss S."xsd:string
http://purl.uniprot.org/citations/23959575http://purl.uniprot.org/core/author"Trautwein C."xsd:string
http://purl.uniprot.org/citations/23959575http://purl.uniprot.org/core/author"Gassler N."xsd:string
http://purl.uniprot.org/citations/23959575http://purl.uniprot.org/core/author"Prinz I."xsd:string
http://purl.uniprot.org/citations/23959575http://purl.uniprot.org/core/author"Lira S.A."xsd:string
http://purl.uniprot.org/citations/23959575http://purl.uniprot.org/core/author"Liedtke C."xsd:string
http://purl.uniprot.org/citations/23959575http://purl.uniprot.org/core/author"Tacke F."xsd:string
http://purl.uniprot.org/citations/23959575http://purl.uniprot.org/core/author"Roskams T."xsd:string
http://purl.uniprot.org/citations/23959575http://purl.uniprot.org/core/author"Luedde T."xsd:string
http://purl.uniprot.org/citations/23959575http://purl.uniprot.org/core/author"Bangen J.M."xsd:string
http://purl.uniprot.org/citations/23959575http://purl.uniprot.org/core/author"Heymann F."xsd:string
http://purl.uniprot.org/citations/23959575http://purl.uniprot.org/core/author"Zimmermann H.W."xsd:string
http://purl.uniprot.org/citations/23959575http://purl.uniprot.org/core/author"Hammerich L."xsd:string
http://purl.uniprot.org/citations/23959575http://purl.uniprot.org/core/author"Govaere O."xsd:string
http://purl.uniprot.org/citations/23959575http://purl.uniprot.org/core/date"2014"xsd:gYear
http://purl.uniprot.org/citations/23959575http://purl.uniprot.org/core/name"Hepatology"xsd:string
http://purl.uniprot.org/citations/23959575http://purl.uniprot.org/core/pages"630-642"xsd:string
http://purl.uniprot.org/citations/23959575http://purl.uniprot.org/core/title"Chemokine receptor CCR6-dependent accumulation of gammadelta T cells in injured liver restricts hepatic inflammation and fibrosis."xsd:string
http://purl.uniprot.org/citations/23959575http://purl.uniprot.org/core/volume"59"xsd:string
http://purl.uniprot.org/citations/23959575http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/23959575
http://purl.uniprot.org/citations/23959575http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/23959575
http://purl.uniprot.org/uniprot/#_A0A087WQB4-mappedCitation-23959575http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/23959575
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