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IL-12 and IL-15 induce the expression of CXCR6 and CD49a on peripheral natural killer cells

IL-12 and IL-15 induce the expression of CXCR6 and CD49a on peripheral natural killer cells
IL-12 and IL-15 induce the expression of CXCR6 and CD49a on peripheral natural killer cells
Murine hepatic NK cells exhibit adaptive features, with liver-specific adhesion molecules CXCR6 and CD49a acting as surface markers. We investigated human liver-resident CXCR6+ and CD49a+ NK cells using RNA sequencing, flow cytometry and functional analysis. We further assessed the role of cytokines in generating NK cells with these phenotypes from the peripheral blood. Hepatic CD49a+ NK cells could be induced using cytokines and produce high quantities of IFNγ and TNFα, in contrast to hepatic CXCR6+ NK cells. RNA sequencing of liver-resident CXCR6+ NK cells confirmed a tolerant immature phenotype with reduced expression of markers associated with maturity and cytotoxicity. Liver-resident double positive CXCR6+CD49a+ hepatic NK cells are immature but maintain high expression of Th1 cytokines as observed for single-positive CD49a+ NK cells. We show that stimulation with activating cytokines can readily induce upregulation of both CD49a and CXCR6 on NK cells in the peripheral blood. In particular IL-12 and IL-15 can generate CXCR6+CD49a+ NK cells in vitro from NK cells isolated from the peripheral blood, with comparable phenotypic and functional features to liver-resident CD49a+ NK cells, including enhanced IFNγ and NKG2C expression. IL-12 and IL-15 may be key for generating NK cells with a tissue-homing phenotype and strong Th1 cytokine profile in the blood, and links peripheral activation of NK cells with tissue-homing. These findings may have important therapeutic implications for immunotherapy of chronic liver disease.
Natural Killer Cells, CD49a antigen, Chemokine Receptor 6 Protein, human, Liver, Cytokines
2050-4527
34-36
Hydes, Theresa
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Noll, Angela
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Salinas-Riester, Gabriela
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Abuhilal, Mohammed Abuhilal
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Armstrong, Thomas
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Hamady, Zaed
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Primrose, John
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Takhar, Arjun
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Walter, Lutz
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Khakoo, Salim
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Hydes, Theresa
d842d1ec-c64a-4934-a5a2-7316fea65767
Noll, Angela
f37365aa-043d-40c7-accf-93c2b5bb1511
Salinas-Riester, Gabriela
77d2eb38-bf0b-466b-b89d-7e82c6dbed72
Abuhilal, Mohammed Abuhilal
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Armstrong, Thomas
fe4be062-3ee3-485a-aef7-6eb9661f50f3
Hamady, Zaed
25ba9e1a-394c-444c-a407-ac0160231af0
Primrose, John
d85f3b28-24c6-475f-955b-ec457a3f9185
Takhar, Arjun
8e6219c4-4014-44e3-8cf7-9621655b6a66
Walter, Lutz
52e3f4b9-0482-49f5-a6a5-f9cd0e3e558d
Khakoo, Salim
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Hydes, Theresa, Noll, Angela, Salinas-Riester, Gabriela, Abuhilal, Mohammed Abuhilal, Armstrong, Thomas, Hamady, Zaed, Primrose, John, Takhar, Arjun, Walter, Lutz and Khakoo, Salim (2018) IL-12 and IL-15 induce the expression of CXCR6 and CD49a on peripheral natural killer cells. Immunity, Inflammation and Disease, 6 (1), 34-36. (doi:10.1002/iid3.190).

Record type: Article

Abstract

Murine hepatic NK cells exhibit adaptive features, with liver-specific adhesion molecules CXCR6 and CD49a acting as surface markers. We investigated human liver-resident CXCR6+ and CD49a+ NK cells using RNA sequencing, flow cytometry and functional analysis. We further assessed the role of cytokines in generating NK cells with these phenotypes from the peripheral blood. Hepatic CD49a+ NK cells could be induced using cytokines and produce high quantities of IFNγ and TNFα, in contrast to hepatic CXCR6+ NK cells. RNA sequencing of liver-resident CXCR6+ NK cells confirmed a tolerant immature phenotype with reduced expression of markers associated with maturity and cytotoxicity. Liver-resident double positive CXCR6+CD49a+ hepatic NK cells are immature but maintain high expression of Th1 cytokines as observed for single-positive CD49a+ NK cells. We show that stimulation with activating cytokines can readily induce upregulation of both CD49a and CXCR6 on NK cells in the peripheral blood. In particular IL-12 and IL-15 can generate CXCR6+CD49a+ NK cells in vitro from NK cells isolated from the peripheral blood, with comparable phenotypic and functional features to liver-resident CD49a+ NK cells, including enhanced IFNγ and NKG2C expression. IL-12 and IL-15 may be key for generating NK cells with a tissue-homing phenotype and strong Th1 cytokine profile in the blood, and links peripheral activation of NK cells with tissue-homing. These findings may have important therapeutic implications for immunotherapy of chronic liver disease.

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Hydes et al 2017 - Accepted Manuscript
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Accepted/In Press date: 11 July 2017
e-pub ahead of print date: 27 September 2017
Published date: March 2018
Keywords: Natural Killer Cells, CD49a antigen, Chemokine Receptor 6 Protein, human, Liver, Cytokines

Identifiers

Local EPrints ID: 414602
URI: https://eprints.soton.ac.uk/id/eprint/414602
ISSN: 2050-4527
PURE UUID: 28d8e121-2c98-4c21-a202-aa4dfb7cd1e5
ORCID for John Primrose: ORCID iD orcid.org/0000-0002-2069-7605

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Date deposited: 04 Oct 2017 16:30
Last modified: 14 Mar 2019 05:36

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Contributors

Author: Theresa Hydes
Author: Angela Noll
Author: Gabriela Salinas-Riester
Author: Mohammed Abuhilal Abuhilal
Author: Thomas Armstrong
Author: Zaed Hamady
Author: John Primrose ORCID iD
Author: Arjun Takhar
Author: Lutz Walter
Author: Salim Khakoo

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