Adoptive transfer of regulatory T cells significantly ameliorated Coxsackievirus B3-induced cardiac fibrosis in mice, a protective effect mediated mainly through the secretion of IL-10.
Does adoptive transfer of regulatory T cells reduce Coxsackievirus B3-induced cardiac fibrosis in BALB/c mice?
Adoptive transfer of regulatory T cells protects against Coxsackievirus B3-induced cardiac fibrosis in a mouse model via IL-10 secretion.
p-value: p=<0.05
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.
Cao et al. (Wed,) conducted a other in Coxsackievirus B3-induced cardiac fibrosis. Adoptive transfer of Regulatory T cells (Tregs) vs. Mock transfer / Isotype antibody was evaluated on Severity of cardiac fibrosis (assessed by collagen volume fraction and collagen I mRNA expression) (p=<0.05). Adoptive transfer of regulatory T cells significantly ameliorated Coxsackievirus B3-induced cardiac fibrosis in mice, a protective effect mediated mainly through the secretion of IL-10.