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


ABSTRACT:

Introduction

Murine hepatic NK cells exhibit adaptive features, with liver-specific adhesion molecules CXCR6 and CD49a acting as surface markers.

Methods

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.

Results

Hepatic CD49a+ NK cells could be induced using cytokines and produce high quantities of IFN? and TNF?, 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 IFN? and NKG2C expression.

Conclusion

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.

SUBMITTER: Hydes T 

PROVIDER: S-EPMC5818449 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Publications

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

Hydes Theresa T   Noll Angela A   Salinas-Riester Gabriela G   Abuhilal Mohammed M   Armstrong Thomas T   Hamady Zaed Z   Primrose John J   Takhar Arjun A   Walter Lutz L   Khakoo Salim I SI  

Immunity, inflammation and disease 20170927 1


<h4>Introduction</h4>Murine hepatic NK cells exhibit adaptive features, with liver-specific adhesion molecules CXCR6 and CD49a acting as surface markers.<h4>Methods</h4>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.<h4>Results</h4>Hepatic CD49a+ NK cells could be induced using cytokines and produce high q  ...[more]

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