title: Adoptive transfer of regulatory T cells protects against Coxsackievirus B3-induced cardiac fibrosis.
abstract: 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute for Immunobiology, Shanghai Medical College, Fudan University, Shanghai, P. R. China.
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Cao
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Sidong
authors.initials: S
authors.lastname: Xiong
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D002452:Cell Count; D029822:Enterovirus B, Human / Q000502:physiology*; D005355:Fibrosis; D016753:Interleukin-10 / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009206:Myocardium / Q000473:pathology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000382:microbiology*
chemical_list: D016753:Interleukin-10
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