Dysregulated CD4+ T Cells and microRNAs in Myocarditis.

Jing Wang,Bo Han

doi:10.3389/fimmu.2020.00539

Abstract

Myocarditis is a polymorphic disease complicated with indeterminate etiology and pathogenesis, and represents one of the most challenging clinical problems lacking specific diagnosis and effective therapy. It is caused by a complex interplay of environmental and genetic factors, and causal links between dysregulated microribonucleic acids (miRNAs) and myocarditis have also been supported by recent epigenetic researches. Both dysregulated CD4+ T cells and miRNAs play critical roles in the pathogenesis of myocarditis, and the classic triphasic model of its pathogenesis consists of the acute infectious, subacute immune, and recovery/chronic myopathic phase. CD4+ T cells are key pathogenic factors underlying the development and progression of myocarditis, and the effector and regulatory subsets, respectively, promote and inhibit autoimmune responses. Furthermore, the reciprocal interplay of these subsets influences the pathogenesis as well. Dysregulated miRNAs along with their mRNA and protein targets have been identified in heart biopsies (intracellular miRNAs) and body fluids (circulating miRNAs) during myocarditis. These miRNAs show phase-dependent changes, and correlate with viral infection, immune status, fibrosis, destruction of cardiomyocytes, arrhythmias, cardiac functions, and outcomes. Thus, miRNAs are promising diagnostic markers and therapeutic targets in myocarditis. In this review, we review myocarditis with an emphasis on its pathogenesis, and present a summary of current knowledge of dysregulated CD4+ T cells and miRNAs in myocarditis.

Highlights

Myocarditis is the inflammation of the myocardium, and a relatively common but potentially lifethreatening disease that affects millions globally, especially pediatric patients and young adults, though it is difficult to gauge the incidence rates [1,2,3,4,5,6,7]
With the development of molecular techniques in recent years, microribonucleic acids (miRNAs) profiles of myocarditis have been analyzed [23], and dysregulated miRNAs along with their mRNA and protein targets have been identified in heart biopsies and body fluids
In the sera of patients with acute myocarditis: high levels of IFN-γ were detected In the endomyocardial biopsies of patients with dilated cardiomyopathy (DCM): genes of IFN-γ were overexpressed In a T cell receptors (TCRs) transgenic mouse model of experimental autoimmune myocarditis (EAM): knocking out IFN-γ receptor or inhibiting its downstream signaling pathway attenuated myocarditis In mice with viral myocarditis (VMC): depletion of IFN-γ during acute infection reduced myocarditis without affecting viral replication In mice infected with T. cruzi: lowering IFN-γ production reduced myocarditis Protect from excessive inflammation In mice with VMC: IFN-γ deficiency led to increased cardiac inflammation In mice with VMC: increased production of IL-1β and tumor necrosis factor (TNF)-α induced myocarditis IL-12 receptor β1-KO mice were resistant to myocarditis induction, which was exacerbated in the wild-type EAM mice treated with exogenous IL-12 [8, 10, 11]

Summary

Introduction

Myocarditis is the inflammation of the myocardium, and a relatively common but potentially lifethreatening disease that affects millions globally, especially pediatric patients and young adults, though it is difficult to gauge the incidence rates [1,2,3,4,5,6,7].

Results

Conclusion