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Fatal eosinophilic myocarditis develops in the absence of IFN-? and IL-17A.

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-?-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-?(-/-)IL-17A(-/-) mice to assess whether IL-17 signaling was responsible for the severe EAM of IFN-?(-/-) mice. Surprisingly, IFN-?(-/-)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-?(-/-)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-? and 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.

SUBMITTER: Barin JG

PROVIDER: S-EPMC3927983 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Fatal eosinophilic myocarditis develops in the absence of IFN-γ and IL-17A.

Barin Jobert G JG Baldeviano G Christian GC Talor Monica V MV Wu Lei L Ong SuFey S Fairweather DeLisa D Bedja Djahida D Stickel Natalie R NR Fontes Jillian A JA Cardamone Ashley B AB Zheng Dongfeng D Gabrielson Kathleen L KL Rose Noel R NR Ciháková Daniela D

Journal of immunology (Baltimore, Md. : 1950) 20130918 8

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 respons ...[more]

PMID: 24048893

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Fatal eosinophilic myocarditis develops in the absence of IFN-? and IL-17A.

Publications

Fatal eosinophilic myocarditis develops in the absence of IFN-γ and IL-17A.

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