Adoptive transfer of regulatory T cells protects against Coxsackievirus B3-induced cardiac fibrosis.

BACKGROUND: Cardiac fibrogenesis in the late stage of viral myocarditis causing contractile dysfunction and ventricular dilatation, is a major pathogenic factor for the progression of myocarditis to serious cardiovascular diseases including dilated cardiomyopathy (DCM) and congestive heart failure (...

Full description

Bibliographic Details
Main Authors: Yanxia Cao, Wei Xu, Sidong Xiong
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3762771?pdf=render
id doaj-7badfa13a5ce435094fc721203a3e4bb
record_format Article
spelling doaj-7badfa13a5ce435094fc721203a3e4bb2020-11-25T02:16:11ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0189e7495510.1371/journal.pone.0074955Adoptive transfer of regulatory T cells protects against Coxsackievirus B3-induced cardiac fibrosis.Yanxia CaoWei XuSidong XiongBACKGROUND: Cardiac fibrogenesis in the late stage of viral myocarditis causing contractile dysfunction and ventricular dilatation, is a major pathogenic factor for the progression of myocarditis to serious cardiovascular diseases including dilated cardiomyopathy (DCM) and congestive heart failure (HF). Recent studies indicate that regulatory T cells (Tregs) are involved in the fibrotic process of liver and lung fibosis. However, the role of Tregs in the development of viral myocarditis-caused cardiac fibrosis and their therapeutic potential remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: Myocardial fibrosis was induced in BALB/c mice by intraperitoneal injection of Coxsackievirus B3 (CVB3) assessed by picrosirius red staining and detection of expression levels of collagen I, matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of metalloproteinase-1 (TIMP-1). Myocardial Treg frequency was down-regulated during the course of viral myocarditis and a negative correlation with the severity of cardiac fibrosis was found. To explore the role of Tregs in CVB-induced cardiac fibrosis, Treg was in vivo depleted by injecting anti-CD25 mAb which resulted in aggravation of cardiac fibrosis. In consistent with that, after adoptive transfer of isolated Tregs into mice, significant amelioration of CVB3-induced cardiac fibrosis was confirmed. Interleukin-10 (IL-10) neutralizing antibodies were used in vivo and in vitro to explore the molecular mechanism of the therapeutic effect of Treg. It was found that administration of anti-IL-10 mAb after Treg transfer abrogated Treg's treating effect and the inhibition of Treg on collagen production by cardiac fibroblasts was mediated mainly through IL-10. CONCLUSION/SIGNIFICANCE: Our data suggested that Tregs have a protective role in the fibrotic process of CVB3-induced cardiac fibrosis via secreting IL-10 and might provide an alternative option for the future treatment of cardiac fibrosis.http://europepmc.org/articles/PMC3762771?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Yanxia Cao
Wei Xu
Sidong Xiong
spellingShingle Yanxia Cao
Wei Xu
Sidong Xiong
Adoptive transfer of regulatory T cells protects against Coxsackievirus B3-induced cardiac fibrosis.
PLoS ONE
author_facet Yanxia Cao
Wei Xu
Sidong Xiong
author_sort Yanxia Cao
title Adoptive transfer of regulatory T cells protects against Coxsackievirus B3-induced cardiac fibrosis.
title_short Adoptive transfer of regulatory T cells protects against Coxsackievirus B3-induced cardiac fibrosis.
title_full Adoptive transfer of regulatory T cells protects against Coxsackievirus B3-induced cardiac fibrosis.
title_fullStr Adoptive transfer of regulatory T cells protects against Coxsackievirus B3-induced cardiac fibrosis.
title_full_unstemmed Adoptive transfer of regulatory T cells protects against Coxsackievirus B3-induced cardiac fibrosis.
title_sort adoptive transfer of regulatory t cells protects against coxsackievirus b3-induced cardiac fibrosis.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2013-01-01
description BACKGROUND: Cardiac fibrogenesis in the late stage of viral myocarditis causing contractile dysfunction and ventricular dilatation, is a major pathogenic factor for the progression of myocarditis to serious cardiovascular diseases including dilated cardiomyopathy (DCM) and congestive heart failure (HF). Recent studies indicate that regulatory T cells (Tregs) are involved in the fibrotic process of liver and lung fibosis. However, the role of Tregs in the development of viral myocarditis-caused cardiac fibrosis and their therapeutic potential remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: Myocardial fibrosis was induced in BALB/c mice by intraperitoneal injection of Coxsackievirus B3 (CVB3) assessed by picrosirius red staining and detection of expression levels of collagen I, matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of metalloproteinase-1 (TIMP-1). Myocardial Treg frequency was down-regulated during the course of viral myocarditis and a negative correlation with the severity of cardiac fibrosis was found. To explore the role of Tregs in CVB-induced cardiac fibrosis, Treg was in vivo depleted by injecting anti-CD25 mAb which resulted in aggravation of cardiac fibrosis. In consistent with that, after adoptive transfer of isolated Tregs into mice, significant amelioration of CVB3-induced cardiac fibrosis was confirmed. Interleukin-10 (IL-10) neutralizing antibodies were used in vivo and in vitro to explore the molecular mechanism of the therapeutic effect of Treg. It was found that administration of anti-IL-10 mAb after Treg transfer abrogated Treg's treating effect and the inhibition of Treg on collagen production by cardiac fibroblasts was mediated mainly through IL-10. CONCLUSION/SIGNIFICANCE: Our data suggested that Tregs have a protective role in the fibrotic process of CVB3-induced cardiac fibrosis via secreting IL-10 and might provide an alternative option for the future treatment of cardiac fibrosis.
url http://europepmc.org/articles/PMC3762771?pdf=render
work_keys_str_mv AT yanxiacao adoptivetransferofregulatorytcellsprotectsagainstcoxsackievirusb3inducedcardiacfibrosis
AT weixu adoptivetransferofregulatorytcellsprotectsagainstcoxsackievirusb3inducedcardiacfibrosis
AT sidongxiong adoptivetransferofregulatorytcellsprotectsagainstcoxsackievirusb3inducedcardiacfibrosis
_version_ 1724892214134308864