title: Tissue-resident Eomes(hi) T-bet(lo) CD56(bright) NK cells with reduced proinflammatory potential are enriched in the adult human liver.
abstract: The adult human liver is enriched with natural killer (NK) cells, accounting for 30-50% of hepatic lymphocytes, which include tissue-resident hepatic NK-cell subpopulations, distinct from peripheral blood NK cells. In murine liver, a subset of liver-resident hepatic NK cells have altered expression of the two highly related T-box transcription factors, T-bet and eomesodermin (Eomes). Here, we investigate the heterogeneity of T-bet and Eomes expression in NK cells from healthy adult human liver with a view to identifying human liver-resident populations. Hepatic NK cells were isolated from donor liver perfusates and biopsies obtained during orthotopic liver transplantation (N = 28). Hepatic CD56(bright) NK cells were Eomes(hi) T-bet(lo) , a phenotype virtually absent from peripheral blood. These NK cells express the chemokine receptor CXCR6 (chemokine (C-X-C motif) receptor 6), a marker of tissue residency, which is absent from hepatic CD56(dim) and blood NK cells. Compared to blood populations, these hepatic CD56(bright) NK cells have increased expression of activatory receptors (NKp44, NKp46, and NKG2D). They show reduced ability to produce IFN-γ but enhanced degranulation in response to challenge with target cells. This functionally distinct population of hepatic NK cells constitutes 20-30% of the total hepatic lymphocyte repertoire and represents a tissue-resident immune cell population adapted to the tolerogenic liver microenvironment.
authors.affiliation: School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
authors.forename: Cathal
authors.initials: C
authors.lastname: Harmon
authors.affiliation: School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Robinson
authors.affiliation: School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
authors.forename: Ronan
authors.initials: R
authors.lastname: Fahey
authors.affiliation: School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
authors.forename: Sarah
authors.initials: S
authors.lastname: Whelan
authors.affiliation: Liver Unit, St. Vincent's University Hospital, Dublin, Ireland.
authors.forename: Diarmaid D
authors.initials: DD
authors.lastname: Houlihan
authors.affiliation: Liver Unit, St. Vincent's University Hospital, Dublin, Ireland.
authors.forename: Justin
authors.initials: J
authors.lastname: Geoghegan
authors.affiliation: School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland. cliona.ofarrelly@tcd.ie.|School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland. cliona.ofarrelly@tcd.ie.
authors.forename: Cliona
authors.initials: C
authors.lastname: O'Farrelly
mesh_terms: D000328:Adult; D015415:Biomarkers; D019002:CD56 Antigen / Q000378:metabolism*; D015550:Cell Degranulation / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D015870:Gene Expression; D006801:Humans; D007108:Immune Tolerance; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016031:Liver Transplantation; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*; D000098815:T-bet Transcription Factor
chemical_list: D015415:Biomarkers; D019002:CD56 Antigen; C491199:EOMES protein, human; C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D007371:Interferon-gamma
keywords: CD56bright natural killer (NK) cells; Human liver; Interferon; Microenvironment; Tissue resident