Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

The paradox of NKp46+ natural killer cells: drivers of severe hepatitis C virus-induced pathology but in-vivo resistance to interferon treatment

Pembroke, Thomas, Christian, Adam, Jones, Emma, Hills, Robert Kerrin, Wang, Edward Chung Yern, Gallimore, Awen Myfanwy and Godkin, Andrew James 2013. The paradox of NKp46+ natural killer cells: drivers of severe hepatitis C virus-induced pathology but in-vivo resistance to interferon treatment. Gut n/a 10.1136/gutjnl-2013-304472

[img]
Preview
PDF - Published Version
Available under License Creative Commons Attribution Non-commercial.

Download (3MB) | Preview

Abstract

Objective: There is evidence that natural killer (NK) cells help control persistent viral infections including hepatitis C virus (HCV). The phenotype and function of blood and intrahepatic NK cells, in steady state and after interferon (IFN) α treatment has not been fully elucidated. Design: We performed a comparison of NK cells derived from blood and intrahepatic compartments in multiple paired samples from patients with a variety of chronic liver diseases. Furthermore, we obtained serial paired samples from an average of five time points in HCV patients treated with IFNα. Results: Liver NK cells demonstrate a distinct activated phenotype compared to blood manifested as downregulation of the NK cell activation receptors CD16, NKG2D, and NKp30; with increased spontaneous degranulation and IFN production. In contrast, NKp46 expression was not downregulated. Indeed, NKp46-rich NK populations were the most activated, correlating closely with the severity of liver inflammation. Following initiation of IFNα treatment there was a significant increase in the proportion of intrahepatic NK cells at days 1 and 3. NKp46-rich NK populations demonstrated no reserve activation capacity with IFNα treatment and were associated with poor viral control on treatment and treatment failure. Conclusions: NKp46 marks out pathologically activated NK cells, which may result from a loss of homeostatic control of activating receptor expression in HCV. Paradoxically these pathological NK cells do not appear to be involved in viral control in IFNα-treated individuals and, indeed, predict slower rates of viral clearance.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QR Microbiology > QR355 Virology
R Medicine > RB Pathology
Additional Information: Online publication date: 11 May 2013.
Publisher: BMJ Publishing Group Ltd
ISSN: 0017-5749
Date of First Compliant Deposit: 30 March 2016
Last Modified: 10 Oct 2017 15:09
URI: http://orca.cf.ac.uk/id/eprint/48533

Citation Data

Cited 34 times in Scopus. View in Scopus. Powered By Scopus® Data

Cited 12 times in Web of Science. View in Web of Science.

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics