Abstract
BackgroundA new subset of T helper (Th) cells, named IL-22-producing Th22 cells, was identified recently. Th22 cells have been implicated in immunity and inflammation. However, the role of these cells in the progression from acute viral myocarditis (AVMC) to dilated cardiomyopathy (DCM) and myocardial fibrosis remains unknown.MethodsBALB/c mice were repeatedly i.p. infected with Coxsackie virus B3 (CVB3) to establish models of AVMC, chronic myocarditis and DCM. On week 2, 12 and 24 post initial injection, the percentage of splenic Th22 cells, the levels of plasma IL-22, cardiac IL-22 receptor (IL-22R) expression, and indicators of myocardial fibrosis were measured. Further, mice with AVMC and chronic myocarditis were treated with an anti-IL-22 neutralizing antibody (Ab). The collagen volume fraction (CVF), the percentage of splenic Th22 cells, plasma IL-22 levels, cardiac IL-22R expression and indicators of myocardial fibrosis were then monitored.ResultsCompared to control mice at the same time points, AVMC, chronic myocarditis and DCM mice have higher percentage of splenic Th22 cells, higher plasma IL-22 levels, increased cardiac IL-22R, as well as increased collagen typeI-A1 (COL1-A1), collagen type III-A1 (COL3-A1) and matrix metalloproteinase-9 (MMP9) expression. However, the expression of tissue inhibitor of metalloproteinase-1(TIMP-1) was decreased. Treatment of AVMC and chronic myocarditis mice with an anti-IL-22 Ab decreased the survival rate and exacerbated myocardial fibrosis. The percentage of splenic Th22 cells, plasma IL-22 levels and cardiac IL-22R expression also decreased in anti-IL-22 Ab treatment group as compared to IgG and PBS treated groups of AVMC and chronic myocarditis mice. Moreover, increased expression of COL1-A1, COL3-A1, MMP9 but decreased expression of TIMP-1 were observed in anti-IL-22 Ab mouse group.ConclusionsTh22 cells play an important role in the pathogenesis of CVB3-induced mouse chronic myocarditis and DCM. IL-22 is a myocardium-protective cytokine by inhibiting myocardial fibrosis. Therefore, Th 22 cells may be considered as potential therapeutic targets for DCM.
Highlights
Viral myocarditis (VMC) is a common cardiac disease, characterized by myocardial inflammation due to virus infection
It has been reported that T helper (Th) 1- and Th17-cell mediated autoimmune destruction may play an important role in myocardial fibrosis in which VMC progresses to dilated cardiomyopathy (DCM)
4 of 20 mice died in the acute viral myocarditis (AVMC) group, 6 of 20 and 11 of 30 mice died in the chronic myocarditis and DCM groups
Summary
Viral myocarditis (VMC) is a common cardiac disease, characterized by myocardial inflammation due to virus infection. It was confirmed that the persistence of viral infection exists in some individuals with chronic myocarditis and dilated cardiomyopathy (DCM). The mechanism of myocardial fibrosis in disease procession has not been elucidated. It has been reported that T helper (Th) 1- and Th17-cell mediated autoimmune destruction may play an important role in myocardial fibrosis in which VMC progresses to DCM. Th1 and Th17 cell subsets may not fully explain the disease mechanism, because results from clinical trial and animal experiments concerning these T cell subsets were inconsistent [5,6,7,8]. The role of these cells in the progression from acute viral myocarditis (AVMC) to dilated cardiomyopathy (DCM) and myocardial fibrosis remains unknown
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
