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 (...
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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 |
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