Journal
DISEASE MODELS & MECHANISMS
Volume 10, Issue 3, Pages 259-270Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dmm.027409
Keywords
Autoimmunity; Dilated cardiomyopathy; Heart disease; Myocarditis; Model; Resiquimod; Toll-like receptor 7/8
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Funding
- British Heart Foundation Cardiovascular Regenerative Medicine Centre [RM/13/1/30157]
- Medical Research Council (via King's College London) UKRMP Immunomodulation Hub [MR/L022699/1]
- ISSF Wellcome Trust 'Value in People Award' [105603/Z/14/Z]
- Jackson Laboratory endowment [TJL-Rosenthal-01]
- Wellcome Trust [105603/Z/14/Z] Funding Source: Wellcome Trust
- British Heart Foundation [FS/15/33/31608, PG/16/93/32345] Funding Source: researchfish
- Medical Research Council [MR/L022699/1, G0901467] Funding Source: researchfish
- MRC [G0901467, MR/L022699/1] Funding Source: UKRI
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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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