Eosinophil-derived IL-4 drives progression of myocarditis to inflammatory dilated cardiomyopathy

Nicola L. Diny, G. Christian Baldeviano, Monica V. Talor, Jobert G. Barin, SuFey Ong, Djahida Bedja, Allison G. Hays, Nisha A. Gilotra, Isabelle Coppens, Noel R. Rose, Daniela Čiháková*

*Corresponding author for this work

Research output: Contribution to journalArticle

30 Citations (Scopus)
4 Downloads (Pure)

Abstract

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.

Original languageEnglish
Pages (from-to)943-957
Number of pages15
JournalJournal of Experimental Medicine
Volume214
Issue number4
DOIs
Publication statusPublished - 1 Apr 2017
Externally publishedYes

Bibliographical note

Copyright the Author(s) 2017. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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