IL-12 and IL-15 induce the expression of CXCR6 and CD49a on peripheral natural killer cells.
Immun Inflamm Dis
; 6(1): 34-46, 2018 03.
Article
em En
| MEDLINE
| ID: mdl-28952190
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 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.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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células Matadoras Naturais
/
Regulação da Expressão Gênica
/
Interleucina-12
/
Interleucina-15
/
Integrina alfa1
/
Receptores CXCR6
/
Fígado
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article