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

Disease Models & Mechanisms

Nicoleta Baxan¹  Daniel J. Stuckey²  Oliver Dent³  Tolani S. Hameed³  Mohammed Bellahcene³  Michael D. Schneider³  Sarah E. Stella³  Susanne Sattler³  Sian E. Harding³  Jane Branca⁴  Ted Duffy⁴  Nadia Rosenthal⁴  Muneer G. Hasham⁴  Bryant Perkins⁴ 

[1] Biological Imaging Centre, Department of Medicine, Imperial College London, London W12 0NN, UK;Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, London WC1E 6DD, UK;National Heart and Lung Institute, Imperial College London, London W12 0NN, UK;The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA;

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

DOI  :  10.1242/dmm.027409

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown