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Interleukin-35 Suppresses Antiviral Immune Response in Chronic Hepatitis B Virus Infection

The mechanisms of hepatitis B virus (HBV) persistent infection are not completely understood. Interleukin (IL)-35, which is a newly identified cytokine belongs to IL-12 family, has been demonstrated to induce immunotolerance. Thus, the aim of current study was to investigate the role of IL-35 during...

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Autores principales: Shao, Xue, Ma, Jingting, Jia, Shengnan, Yang, Lanlan, Wang, Wudong, Jin, Zhenjing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5693856/
https://www.ncbi.nlm.nih.gov/pubmed/29181338
http://dx.doi.org/10.3389/fcimb.2017.00472
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author Shao, Xue
Ma, Jingting
Jia, Shengnan
Yang, Lanlan
Wang, Wudong
Jin, Zhenjing
author_facet Shao, Xue
Ma, Jingting
Jia, Shengnan
Yang, Lanlan
Wang, Wudong
Jin, Zhenjing
author_sort Shao, Xue
collection PubMed
description The mechanisms of hepatitis B virus (HBV) persistent infection are not completely understood. Interleukin (IL)-35, which is a newly identified cytokine belongs to IL-12 family, has been demonstrated to induce immunotolerance. Thus, the aim of current study was to investigate the role of IL-35 during chronic HBV infection. A total of 61 patients with chronic HBV infection [37 chronic hepatitis B (CHB) and 24 asymptomatic HBV carriers (ASC)] and 20 healthy individuals were enrolled. IL-35 concentration as well as the modulatory function of IL-35 on CD4(+)CD25(+)CD127(dim/−) regulatory T cells (Tregs) and on HBV antigen-specific CD8(+) T cells was investigated. IL-35 expression was significantly increased in both CHB and ASC, and was positively correlated with the levels of HBV DNA. Inhibition of viral replication induced the reduction in serum levels of IL-35. IL-35 stimulation led to inhibition of proinflammatory cytokine productions and elevation of apoptosis in peripheral blood mononuclear cells (PBMCs), but not in HepG2.2.15 cells. Moreover, IL-35 stimulation not only robustly inhibited cellular proliferation, but also up-regulated the production of IL-10 and IL-35 in a HBV antigen-specific and non-specific manner in Tregs/CD4(+)CD25(−) T cells coculture system, which indicated enhancement of suppressive function of Tregs. Furthermore, IL-35 also reduced both cytolytic activity (direct lysis of HepG2.2.15 cells) and noncytolytic function (IFN-γ and TNF-α production) of HBV antigen-specific CD8(+) T cells. The current data suggested that IL-35 contributed to maintain viral persistence by suppressing antiviral immune responses and reducing inflammatory responses in chronic HBV infection.
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spelling pubmed-56938562017-11-27 Interleukin-35 Suppresses Antiviral Immune Response in Chronic Hepatitis B Virus Infection Shao, Xue Ma, Jingting Jia, Shengnan Yang, Lanlan Wang, Wudong Jin, Zhenjing Front Cell Infect Microbiol Microbiology The mechanisms of hepatitis B virus (HBV) persistent infection are not completely understood. Interleukin (IL)-35, which is a newly identified cytokine belongs to IL-12 family, has been demonstrated to induce immunotolerance. Thus, the aim of current study was to investigate the role of IL-35 during chronic HBV infection. A total of 61 patients with chronic HBV infection [37 chronic hepatitis B (CHB) and 24 asymptomatic HBV carriers (ASC)] and 20 healthy individuals were enrolled. IL-35 concentration as well as the modulatory function of IL-35 on CD4(+)CD25(+)CD127(dim/−) regulatory T cells (Tregs) and on HBV antigen-specific CD8(+) T cells was investigated. IL-35 expression was significantly increased in both CHB and ASC, and was positively correlated with the levels of HBV DNA. Inhibition of viral replication induced the reduction in serum levels of IL-35. IL-35 stimulation led to inhibition of proinflammatory cytokine productions and elevation of apoptosis in peripheral blood mononuclear cells (PBMCs), but not in HepG2.2.15 cells. Moreover, IL-35 stimulation not only robustly inhibited cellular proliferation, but also up-regulated the production of IL-10 and IL-35 in a HBV antigen-specific and non-specific manner in Tregs/CD4(+)CD25(−) T cells coculture system, which indicated enhancement of suppressive function of Tregs. Furthermore, IL-35 also reduced both cytolytic activity (direct lysis of HepG2.2.15 cells) and noncytolytic function (IFN-γ and TNF-α production) of HBV antigen-specific CD8(+) T cells. The current data suggested that IL-35 contributed to maintain viral persistence by suppressing antiviral immune responses and reducing inflammatory responses in chronic HBV infection. Frontiers Media S.A. 2017-11-13 /pmc/articles/PMC5693856/ /pubmed/29181338 http://dx.doi.org/10.3389/fcimb.2017.00472 Text en Copyright © 2017 Shao, Ma, Jia, Yang, Wang and Jin. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Shao, Xue
Ma, Jingting
Jia, Shengnan
Yang, Lanlan
Wang, Wudong
Jin, Zhenjing
Interleukin-35 Suppresses Antiviral Immune Response in Chronic Hepatitis B Virus Infection
title Interleukin-35 Suppresses Antiviral Immune Response in Chronic Hepatitis B Virus Infection
title_full Interleukin-35 Suppresses Antiviral Immune Response in Chronic Hepatitis B Virus Infection
title_fullStr Interleukin-35 Suppresses Antiviral Immune Response in Chronic Hepatitis B Virus Infection
title_full_unstemmed Interleukin-35 Suppresses Antiviral Immune Response in Chronic Hepatitis B Virus Infection
title_short Interleukin-35 Suppresses Antiviral Immune Response in Chronic Hepatitis B Virus Infection
title_sort interleukin-35 suppresses antiviral immune response in chronic hepatitis b virus infection
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5693856/
https://www.ncbi.nlm.nih.gov/pubmed/29181338
http://dx.doi.org/10.3389/fcimb.2017.00472
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