Fatal eosinophilic myocarditis develops in the absence of IFN-γand IL-17A

Jobert G. Barin, G. Christian Baldeviano, Monica V. Talor, Lei Wu, Su Fey Ong, Lisa De Fairweather, Djahida Bedja, Natalie R. Stickel, Jillian A. Fontes, Ashley B. Cardamone, Dongfeng Zheng, Kathleen L. Gabrielson, Noel R. Rose, Daniela Čiháková*

*Corresponding author for this work

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

CD4+ T cells play a central role in inflammatory heart disease, implicating a cytokine product associated with Th cell effector function as a necessary mediator of this pathophysiology. IFN-γ-deficient mice developed severe experimental autoimmune myocarditis (EAM), in which mice are immunized with cardiac myosin peptide, whereas IL-17A-deficient mice were protected from progression to dilated cardiomyopathy. We generated IFN-γ-/- IL-17A-/- mice to assess whether IL-17 signaling was responsible for the severe EAM of IFN-γ-/- mice. Surprisingly, IFN-γ-/- IL-17A-/- mice developed a rapidly fatal EAM. Eosinophils constituted a third of infiltrating leukocytes, qualifying this disease as eosinophilic myocarditis. We found increased cardiac production of CCL11/eotaxin, as well as Th2 deviation, among heart-infiltrating CD4 + cells. Ablation of eosinophil development improved survival of IFN-γ-/- IL-17A-/- mice, demonstrating the necessity of eosinophils in fatal heart failure. The severe and rapidly fatal autoimmune inflammation that developed in the combined absence of IFN-γand IL-17A constitutes a novel model of eosinophilic heart disease in humans. This is also, to our knowledge, the first demonstration that eosinophils have the capacity to act as necessary mediators of morbidity in an autoimmune process.

Original languageEnglish
Pages (from-to)4038-4047
Number of pages10
JournalJournal of Immunology
Volume191
Issue number8
DOIs
Publication statusPublished - 15 Oct 2013
Externally publishedYes

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