TY - JOUR
T1 - Fatal eosinophilic myocarditis develops in the absence of IFN-γand IL-17A
AU - Barin, Jobert G.
AU - Baldeviano, G. Christian
AU - Talor, Monica V.
AU - Wu, Lei
AU - Ong, Su Fey
AU - De Fairweather, Lisa
AU - Bedja, Djahida
AU - Stickel, Natalie R.
AU - Fontes, Jillian A.
AU - Cardamone, Ashley B.
AU - Zheng, Dongfeng
AU - Gabrielson, Kathleen L.
AU - Rose, Noel R.
AU - Čiháková, Daniela
PY - 2013/10/15
Y1 - 2013/10/15
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.1301282
DO - 10.4049/jimmunol.1301282
M3 - Article
C2 - 24048893
AN - SCOPUS:84885444778
SN - 0022-1767
VL - 191
SP - 4038
EP - 4047
JO - Journal of Immunology
JF - Journal of Immunology
IS - 8
ER -