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...

Celý popis

Uloženo v:
Podrobná bibliografie
Vydáno v:Journal of virology Ročník 87; číslo 21; s. 11626
Hlavní autoři: Wang, Jia M, Cheng, Yong Q, Shi, Lei, Ying, Ruo S, Wu, Xiao Y, Li, Guang Y, Moorman, Jonathan P, Yao, Zhi Q
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 01.11.2013
Témata:
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
On-line přístup:Zjistit podrobnosti o přístupu
Tagy: Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
Popis
Shrnutí: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.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1098-5514
1098-5514
DOI:10.1128/JVI.01515-13