Fatal Eosinophilic Myocarditis Develops in the Absence of IFN-γ and IL-17A

被引：48

作者：

Barin, Jobert G. ^{[1
,2
,3
]}

Baldeviano, G. Christian ^{[3
,4
]}

Talor, Monica V. ^{[2
]}

Wu, Lei ^{[3
]}

Ong, SuFey ^{[3
]}

Fairweather, DeLisa ^{[5
]}

Bedja, Djahida ^{[6
]}

Stickel, Natalie R. ^{[7
]}

Fontes, Jillian A. ^{[3
]}

Cardamone, Ashley B. ^{[2
]}

Zheng, Dongfeng ^{[2
]}

Gabrielson, Kathleen L. ^{[6
]}

Rose, Noel R. ^{[1
,2
,3
]}

Cihakova, Daniela ^{[2
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Immunol Training Program, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA

[3] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, William H Feinstone Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA

[4] US Naval Med Res Unit Six NAMRU 6, Dept Parasitol, Lima, Peru

[5] Johns Hopkins Univ, Dept Environm Hlth Sci, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA

[6] Johns Hopkins Univ, Sch Med, Dept Comparat Med, Baltimore, MD 21205 USA

[7] Univ Freiburg, Dept Hematol & Oncol, D-79106 Freiburg, Germany

来源：

JOURNAL OF IMMUNOLOGY | 2013年 / 191卷 / 08期

基金：

美国国家卫生研究院;

关键词：

EXPERIMENTAL AUTOIMMUNE MYOCARDITIS; COXSACKIEVIRUS-INDUCED MYOCARDITIS; INTERLEUKIN-17; FAMILY-MEMBERS; REGULATORY T-CELLS; INTERFERON-GAMMA; TOXOCARA-CANIS; TH17; CELLS; IN-VIVO; MICE; DISEASE;

D O I：

10.4049/jimmunol.1301282

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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-gamma-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-gamma-/-IL-17A(-/-) mice to assess whether IL-17 signaling was responsible for the severe EAM of IFN-gamma(-/-) mice. Surprisingly, IFN-gamma-/-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-gamma(-/-)2/2 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-gamma 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.

引用

页码：4038 / 4047

页数：10

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