Eosinophil deficiency or eosinophil-specific IL-4 deletion protected mice from progressing from experimental autoimmune myocarditis to inflammatory dilated cardiomyopathy.
Does eosinophil-derived IL-4 drive the progression of experimental autoimmune myocarditis to inflammatory dilated cardiomyopathy?
Eosinophils drive the progression of myocarditis to inflammatory dilated cardiomyopathy through the production of IL-4 in a mouse model.
Inflammatory dilated cardiomyopathy (DCMi) is a major cause of heart failure in children and young adults. DCMi develops in up to 30% of myocarditis patients, but the mechanisms involved in disease progression are poorly understood. Patients with eosinophilia frequently develop cardiomyopathies. In this study, we used the experimental autoimmune myocarditis (EAM) model to determine the role of eosinophils in myocarditis and DCMi. Eosinophils were dispensable for myocarditis induction but were required for progression to DCMi. Eosinophil-deficient ΔdblGATA1 mice, in contrast to WT mice, showed no signs of heart failure by echocardiography. Induction of EAM in hypereosinophilic IL-5Tg mice resulted in eosinophilic myocarditis with severe ventricular and atrial inflammation, which progressed to severe DCMi. This was not a direct effect of IL-5, as IL-5TgΔdblGATA1 mice were protected from DCMi, whereas IL-5−/− mice exhibited DCMi comparable with WT mice. Eosinophils drove progression to DCMi through their production of IL-4. Our experiments showed eosinophils were the major IL-4–expressing cell type in the heart during EAM, IL-4−/− mice were protected from DCMi like ΔdblGATA1 mice, and eosinophil-specific IL-4 deletion resulted in improved heart function. In conclusion, eosinophils drive progression of myocarditis to DCMi, cause severe DCMi when present in large numbers, and mediate this process through IL-4.
Diny et al. (Thu,) conducted a other in Myocarditis and inflammatory dilated cardiomyopathy. Eosinophil deficiency or eosinophil-specific IL-4 deletion vs. Wild-type mice was evaluated on Progression to inflammatory dilated cardiomyopathy and heart failure. Eosinophil deficiency or eosinophil-specific IL-4 deletion protected mice from progressing from experimental autoimmune myocarditis to inflammatory dilated cardiomyopathy.