Abstract Title:

Hepatocyte-derived exosomes promote T follicular regulatory cell expansion during HCV infection.

Abstract Source:

Hepatology. 2017 Jul 27. Epub 2017 Jul 27. PMID: 28749570

Abstract Author(s):

Dustin A Cobb, Lucy Golden-Mason, Hugo R Rosen, Young S Hahn

Article Affiliation:

Dustin A Cobb


: Hepatitis C virus (HCV) is a global health concern that can cause severe liver disease such as cirrhosis and hepatocellular carcinoma. Control of HCV requires vigorous T cell responses, yet CD4(+) T cells in chronic HCV patients are dysfunctional. T follicular regulatory (Tfr) cells are a subset of regulatory T cells that suppress T follicular helper (Tfh) cells and the generation of high affinity antibody-producing B cells. In this study, we examined the accumulation of Tfr cells in the liver compartment during chronic HCV infection and defined the cellular and molecular mechanisms underlying their expansion. Our analysis revealed a substantial population of Tfr cells in the livers of chronic HCV patients that is absent in liver tissues from non-viral hepatitis or healthy subjects. Co-culture of PBMCs from healthy subjects with HCV-infected hepatoma cells resulted in preferential expansion of circulating Tfr cells leading to the suppression of Tfh cells. Additionally, co-culture of tonsillar cells with infected hepatoma cells lead to an expansion of germinal center Tfr. Notably, expansion was mediated by TGF-β-containing exosomes released from HCV-infected hepatocytes as blockade of exosome-associated TGF-β or inhibition of exosome release abrogated Tfr expansion.

CONCLUSION: These results show that liver-derived exosomes play a pivotal role in the accumulation of Tfr cells, likely leading to suppression of Tfh responses in HCV-infected patients. Our study identifies a novel pathway in which HCV infection in hepatocytes exacerbates Tfr cell responses to subvert antiviral immunity. This article is protected by copyright. All rights reserved.

Study Type : Human Study
Additional Links
Additional Keywords : Exosomes : CK(35) : AC(10)

Print Options

Key Research Topics

Sayer Ji
Founder of GreenMedInfo.com

Subscribe to our informative Newsletter & get Nature's Evidence-Based Pharmacy

Our newsletter serves 500,000 with essential news, research & healthy tips, daily.

Download Now

500+ pages of Natural Medicine Alternatives and Information.

This website is for information purposes only. By providing the information contained herein we are not diagnosing, treating, curing, mitigating, or preventing any type of disease or medical condition. Before beginning any type of natural, integrative or conventional treatment regimen, it is advisable to seek the advice of a licensed healthcare professional.

© Copyright 2008-2021 GreenMedInfo.com, Journal Articles copyright of original owners, MeSH copyright NLM.