Interleukin-13 protects against experimental autoimmune myocarditis by regulating macrophage differentiation

Daniela Cihakova, Jobert G. Barin, Marina Afanasyeva, Miho Kimura, De Lisa Fairweather, Michael Berg, Monica V. Talor, G. Christian Baldeviano, Sylvia Frisancho, Kathleen Gabrielson, Djahida Bedja, Noel R. Rose

Research output: Contribution to journalArticle

100 Scopus citations

Abstract

We report here that interleukin (IL)-13 protects BALB/c mice from myocarditis, whether induced by peptide immunization or by viral infection. In contrast to mild disease in IL-4 knockout (KO) BALB/c mice, IL-13 KO BALB/c mice developed severe coxsackievirus B3 (CVB3)-induced autoimmune myocarditis and myocarditogenic peptide-induced experimental autoimmune myocarditis. Such severe disease was characterized by increased cardiac inflammation, increased total intracardiac CD45+ leukocytes, elevated anti-cardiac myosin autoantibodies, and increased cardiac fibrosis. Echocardiography revealed that IL-13 KO mice developed severe dilated cardiomyopathy with impaired cardiac function and heart failure. Hearts of IL-13 KO mice had increased levels of the proinflammatory and profibrotic cytokines IL-1β, IL-18, interferon-γ, transforming growth factor-β1, and IL-4 as well as histamine. The hallmark of the disease in IL-13 KO mice was the up-regulation of T-cell responses. CD4+ T cells were increased in IL-13 KO hearts both proportionally and in absolute number. Splenic T cells from IL-13 KO mice were highly activated, and myosin stimulation additionally increased T-cell proliferation. CD4+CD25+Foxp3+ regulatory T-cell numbers were decreased in the spleens of IL-13 KO mice. IL-13 deficiency led to decreased levels of alternatively activated CD206+ and CD204+ macrophages and increased levels of classically activated macrophages. IL-13 KO mice had increased caspase-1 activation, leading to increased production of both IL-1β and IL-18. Therefore, IL-13 protects against myocarditis by modulating monocyte/macrophage populations and by regulating their function.

Original languageEnglish (US)
Pages (from-to)1195-1208
Number of pages14
JournalAmerican Journal of Pathology
Volume172
Issue number5
DOIs
StatePublished - May 2008

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Fingerprint Dive into the research topics of 'Interleukin-13 protects against experimental autoimmune myocarditis by regulating macrophage differentiation'. Together they form a unique fingerprint.

  • Cite this

    Cihakova, D., Barin, J. G., Afanasyeva, M., Kimura, M., Fairweather, D. L., Berg, M., Talor, M. V., Baldeviano, G. C., Frisancho, S., Gabrielson, K., Bedja, D., & Rose, N. R. (2008). Interleukin-13 protects against experimental autoimmune myocarditis by regulating macrophage differentiation. American Journal of Pathology, 172(5), 1195-1208. https://doi.org/10.2353/ajpath.2008.070207