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

TLR7/8 激动剂 Resiquimod 诱发的全身自身免疫在新型自身免疫性心脏病小鼠模型中导致心肌炎和扩张型心肌病

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作者:Muneer G Hasham, Nicoleta Baxan, Daniel J Stuckey, Jane Branca, Bryant Perkins, Oliver Dent, Ted Duffy, Tolani S Hameed, Sarah E Stella, Mohammed Bellahcene, Michael D Schneider, Sian E Harding, Nadia Rosenthal, Susanne Sattler

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.

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