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    Tissue-resident Eomes(hi) T-bet(lo) CD56(bright) NK cells with reduced proinflammatory potential are enriched in the adult human liver


    Harmon, Cathal and Robinson, Mark W. and Fahey, Ronan and Whelan, Sarah and Houlihan, Diarmaid D. and Geoghegan, Justin and O'Farrelly, Cliona (2016) Tissue-resident Eomes(hi) T-bet(lo) CD56(bright) NK cells with reduced proinflammatory potential are enriched in the adult human liver. European Journal of Immunology, 46 (9). ISSN 1521-4141

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    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-residentpopulations.HepaticNKcellswereisolatedfromdonorliverperfusatesand biopsies obtained during orthotopic liver transplantation (N = 28). Hepatic CD56bright NK cells were Eomeshi T-betlo, 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 CD56dim and blood NK cells. Compared to blood populations, these hepatic CD56bright 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.

    Item Type: Article
    Keywords: CD56(bright); natural killer (NK) cells; Human liver; Interferon; Microenvironment; Tissue resident;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 12654
    Identification Number: doi.org/10.1002/eji.201646559
    Depositing User: Mark Robinson
    Date Deposited: 27 Mar 2020 12:10
    Journal or Publication Title: European Journal of Immunology
    Publisher: Wiley-VCH Verlag
    Refereed: Yes
    URI:

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