PMID- 24023968
OWN - NLM
STAT- MEDLINE
DCOM- 20140408
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 9
DP  - 2013
TI  - Adoptive transfer of regulatory T cells protects against Coxsackievirus 
      B3-induced cardiac fibrosis.
PG  - e74955
LID - 10.1371/journal.pone.0074955 [doi]
LID - e74955
AB  - 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.
FAU - Cao, Yanxia
AU  - Cao Y
AD  - Institute for Immunobiology, Shanghai Medical College, Fudan University, 
      Shanghai, P. R. China.
FAU - Xu, Wei
AU  - Xu W
FAU - Xiong, Sidong
AU  - Xiong S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130904
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 130068-27-8 (Interleukin-10)
SB  - IM
MH  - *Adoptive Transfer
MH  - Animals
MH  - Cell Count
MH  - Enterovirus B, Human/*physiology
MH  - Fibrosis
MH  - Interleukin-10/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Myocardium/*pathology
MH  - T-Lymphocytes, Regulatory/cytology/*microbiology
PMC - PMC3762771
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/09/12 06:00
MHDA- 2014/04/09 06:00
PMCR- 2013/09/04
CRDT- 2013/09/12 06:00
PHST- 2013/06/25 00:00 [received]
PHST- 2013/08/07 00:00 [accepted]
PHST- 2013/09/12 06:00 [entrez]
PHST- 2013/09/12 06:00 [pubmed]
PHST- 2014/04/09 06:00 [medline]
PHST- 2013/09/04 00:00 [pmc-release]
AID - PONE-D-13-26195 [pii]
AID - 10.1371/journal.pone.0074955 [doi]
PST - epublish
SO  - PLoS One. 2013 Sep 4;8(9):e74955. doi: 10.1371/journal.pone.0074955. eCollection 
      2013.