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CXCR6 marks a novel subset of T-bet(lo)Eomes(hi) natural killer cells residing in human liver

Stegmann, KA; Robertson, F; Hansi, N; Gill, U; Pallant, C; Christophides, T; Pallett, LJ; ... Maini, MK; + view all (2016) CXCR6 marks a novel subset of T-bet(lo)Eomes(hi) natural killer cells residing in human liver. Scientific Reports , 6 , Article ARTN 261. 10.1038/srep26157. Green open access

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Abstract

Natural killer cells (NK) are highly enriched in the human liver, where they can regulate immunity and immunopathology. We probed them for a liver-resident subset, distinct from conventional bone-marrow-derived NK. CXCR6+ NK were strikingly enriched in healthy and diseased liver compared to blood (p < 0.0001). Human hepatic CXCR6+ NK had an immature phenotype (predominantly CD56brightCD16−CD57−), and expressed the tissue-residency marker CD69. CXCR6+ NK produced fewer cytotoxic mediators and pro-inflammatory cytokines than the non-liver-specific CXCR6− fraction. Instead CXCR6+ NK could upregulate TRAIL, a key death ligand in hepatitis pathogenesis. CXCR6 demarcated liver NK into two transcriptionally distinct populations: T-bethiEomeslo(CXCR6−) and T-betloEomeshi(CXCR6+); the latter was virtually absent in the periphery. The small circulating CXCR6+ subset was predominantly T-bethiEomeslo, suggesting its lineage was closer to CXCR6− peripheral than CXCR6+ liver NK. These data reveal a large subset of human liver-resident T-betloEomeshi NK, distinguished by their surface expression of CXCR6, adapted for hepatic tolerance and inducible anti-viral immunity.

Type: Article
Title: CXCR6 marks a novel subset of T-bet(lo)Eomes(hi) natural killer cells residing in human liver
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/srep26157
Publisher version: http://dx.doi.org/10.1038/srep26157
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, CHRONIC HEPATITIS-B, NK CELLS, T-CELLS, VIRUS INFECTION, MEMORY, EOMES, BET, CYTOTOXICITY, INFLAMMATION, RESPONSES
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Surgical Biotechnology
URI: https://discovery.ucl.ac.uk/id/eprint/1498456
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