KLRG1 negatively regulates natural killer cell functions through the Akt pathway in individuals with chronic hepatitis C virus infection

In this study, we demonstrate that killer cell lectin-like receptor subfamily G member 1 (KLRG1), a transmembrane protein preferentially expressed on T cells, is highly expressed on CD56(+) NK cells, which are significantly reduced in their numbers and functions in the peripheral blood of patients w...

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Bibliographic Details
Published in:Journal of virology Vol. 87; no. 21; p. 11626
Main Authors: Wang, Jia M, Cheng, Yong Q, Shi, Lei, Ying, Ruo S, Wu, Xiao Y, Li, Guang Y, Moorman, Jonathan P, Yao, Zhi Q
Format: Journal Article
Language:English
Published: United States 01.11.2013
Subjects:
Apoptosis
CD56 Antigen - analysis
Cell Proliferation
Female
Hepatitis C, Chronic - immunology
Humans
Interferon-gamma - secretion
Killer Cells, Natural - chemistry
Killer Cells, Natural - immunology
Lectins, C-Type - metabolism
Male
Signal Transduction
Trans-Activators - metabolism
ISSN:1098-5514, 1098-5514
Online Access:Get more information
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Summary:In this study, we demonstrate that killer cell lectin-like receptor subfamily G member 1 (KLRG1), a transmembrane protein preferentially expressed on T cells, is highly expressed on CD56(+) NK cells, which are significantly reduced in their numbers and functions in the peripheral blood of patients with chronic hepatitis C virus (HCV) infection compared to subjects without infection. KLRG1 expression is also upregulated on healthy NK cells exposed to Huh-7 hepatocytes infected with HCV in vitro. Importantly, the expression levels of KLRG1 are inversely associated with the capacity of NK cells to proliferate and to produce gamma interferon (IFN-γ) but positively associated with apoptosis of NK cells in response to inflammatory cytokine stimulation. KLRG1(+) NK cells, including CD56(bright) and CD56(dim) subsets, exhibit impaired cell activation and IFN-γ production but increased apoptosis compared to KLRG1(-) NK cells, particularly in HCV-infected individuals. Importantly, blockade of KLRG1 signaling significantly recovered the impaired IFN-γ production by NK cells from HCV-infected subjects. Blockade of KLRG1 also enhanced the impaired phosphorylation of Akt (Ser473) in NK cells from HCV-infected subjects. Taken together, these results indicate that KLRG1 negatively regulates NK cell numbers and functions via the Akt pathway, thus providing a novel marker and therapeutic target for HCV infection.
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ISSN:1098-5514
1098-5514
DOI:10.1128/JVI.01515-13