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http://purl.uniprot.org/citations/26396175http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/26396175http://www.w3.org/2000/01/rdf-schema#comment"

Unlabelled

Primary biliary cirrhosis (PBC) is a chronic cholestatic disease of unknown etiopathogenesis showing progressive autoimmune-mediated cholangitis. In PBC patients, the liver and lymphocytes exhibit diminished expression of AE2/SLC4A2, a Cl-/HCO3-anion exchanger involved in biliary bicarbonate secretion and intracellular pH regulation. Decreased AE2 expression may be pathogenic as Ae2a,b(-/-) mice reproduce hepatobiliary and immunological features resembling PBC. To understand the role of AE2 deficiency for autoimmunity predisposition we focused on the phenotypic changes of T cells that occur over the life-span of Ae2a,b(-/-) mice. At early ages (1-9 months), knockout mice had reduced numbers of intrahepatic T cells, which exhibited increased activation, programmed-cell-death (PD)-1 expression, and apoptosis. Moreover, young knockouts had upregulated PD-1 ligand (PD-L1) on bile-duct cells, and administration of neutralizing anti-PD-L1 antibodies prevented their intrahepatic T-cell deletion. Older (≥ 10 months) knockouts, however, showed intrahepatic accumulation of cytotoxic CD8(+) T cells with downregulated PD-1 and diminished apoptosis. In-vitro DNA demethylation with 5-aza-2'-deoxycytidine partially reverted PD-1 downregulation of intrahepatic CD8(+) T cells from aged knockouts.

Conclusion

Early in life, AE2 deficiency results in intrahepatic T-cell activation and PD-1/PD-L1 mediated deletion. With aging, intrahepatic CD8+ T cells epigenetically suppress PD-1, and their consequential expansion and further activation favor autoimmune cholangitis."xsd:string
http://purl.uniprot.org/citations/26396175http://purl.org/dc/terms/identifier"doi:10.18632/oncotarget.5665"xsd:string
http://purl.uniprot.org/citations/26396175http://purl.uniprot.org/core/author"Ferrer A."xsd:string
http://purl.uniprot.org/citations/26396175http://purl.uniprot.org/core/author"Prieto J."xsd:string
http://purl.uniprot.org/citations/26396175http://purl.uniprot.org/core/author"Saez E."xsd:string
http://purl.uniprot.org/citations/26396175http://purl.uniprot.org/core/author"Oude Elferink R.P."xsd:string
http://purl.uniprot.org/citations/26396175http://purl.uniprot.org/core/author"Concepcion A.R."xsd:string
http://purl.uniprot.org/citations/26396175http://purl.uniprot.org/core/author"Hervas-Stubbs S."xsd:string
http://purl.uniprot.org/citations/26396175http://purl.uniprot.org/core/author"Medina J.F."xsd:string
http://purl.uniprot.org/citations/26396175http://purl.uniprot.org/core/author"Portu A."xsd:string
http://purl.uniprot.org/citations/26396175http://purl.uniprot.org/core/author"Salas J.T."xsd:string
http://purl.uniprot.org/citations/26396175http://purl.uniprot.org/core/author"Sarvide S."xsd:string
http://purl.uniprot.org/citations/26396175http://purl.uniprot.org/core/author"Uriarte I."xsd:string
http://purl.uniprot.org/citations/26396175http://purl.uniprot.org/core/date"2015"xsd:gYear
http://purl.uniprot.org/citations/26396175http://purl.uniprot.org/core/name"Oncotarget"xsd:string
http://purl.uniprot.org/citations/26396175http://purl.uniprot.org/core/pages"28588-28606"xsd:string
http://purl.uniprot.org/citations/26396175http://purl.uniprot.org/core/title"CD8+ T cells undergo activation and programmed death-1 repression in the liver of aged Ae2a,b-/- mice favoring autoimmune cholangitis."xsd:string
http://purl.uniprot.org/citations/26396175http://purl.uniprot.org/core/volume"6"xsd:string
http://purl.uniprot.org/citations/26396175http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/26396175
http://purl.uniprot.org/citations/26396175http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/26396175
http://purl.uniprot.org/uniprot/#_A0A0R4J101-mappedCitation-26396175http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26396175
http://purl.uniprot.org/uniprot/#_P13808-mappedCitation-26396175http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26396175
http://purl.uniprot.org/uniprot/#_A0A0R4J1K4-mappedCitation-26396175http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26396175
http://purl.uniprot.org/uniprot/#_A0A0R4J1K9-mappedCitation-26396175http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26396175
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