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Dis Model Mech. 2017 Mar 1;10(3):259-270. doi: 10.1242/dmm.027409.

Systemic autoimmunity induced by the TLR7/8 agonist Resiquimod causes myocarditis and dilated cardiomyopathy in a new mouse model of autoimmune heart disease.

Author information

1
The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA.
2
Biological Imaging Centre, Department of Medicine, Imperial College London, London W12 0NN, UK.
3
Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, London WC1E 6DD, UK.
4
National Heart and Lung Institute, Imperial College London, London W12 0NN, UK.
5
National Heart and Lung Institute, Imperial College London, London W12 0NN, UK s.sattler@imperial.ac.uk.

Abstract

Systemic autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) show significant heart involvement and cardiovascular morbidity, which can be due to systemically increased levels of inflammation or direct autoreactivity targeting cardiac tissue. Despite high clinical relevance, cardiac damage secondary to systemic autoimmunity lacks inducible rodent models. Here, we characterise immune-mediated cardiac tissue damage in a new model of SLE induced by topical application of the Toll-like receptor 7/8 (TLR7/8) agonist Resiquimod. We observe a cardiac phenotype reminiscent of autoimmune-mediated dilated cardiomyopathy, and identify auto-antibodies as major contributors to cardiac tissue damage. Resiquimod-induced heart disease is a highly relevant mouse model for mechanistic and therapeutic studies aiming to protect the heart during autoimmunity.

KEYWORDS:

Autoimmunity; Dilated cardiomyopathy; Heart disease; Model; Myocarditis; Resiquimod; Toll-like receptor 7/8

PMID:
28250051
PMCID:
PMC5374321
DOI:
10.1242/dmm.027409
[Indexed for MEDLINE]
Free PMC Article

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