title: Systemic autoimmunity induced by the TLR7/8 agonist Resiquimod causes myocarditis and dilated cardiomyopathy in a new mouse model of autoimmune heart disease.
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.
authors.affiliation: The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA.
authors.forename: Muneer G
authors.initials: MG
authors.lastname: Hasham
authors.affiliation: Biological Imaging Centre, Department of Medicine, Imperial College London, London W12 0NN, UK.
authors.forename: Nicoleta
authors.initials: N
authors.lastname: Baxan
authors.affiliation: Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, London WC1E 6DD, UK.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Stuckey
authors.affiliation: The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA.
authors.forename: Jane
authors.initials: J
authors.lastname: Branca
authors.affiliation: The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA.
authors.forename: Bryant
authors.initials: B
authors.lastname: Perkins
authors.affiliation: National Heart and Lung Institute, Imperial College London, London W12 0NN, UK.
authors.forename: Oliver
authors.initials: O
authors.lastname: Dent
authors.affiliation: The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA.
authors.forename: Ted
authors.initials: T
authors.lastname: Duffy
authors.affiliation: National Heart and Lung Institute, Imperial College London, London W12 0NN, UK.
authors.forename: Tolani S
authors.initials: TS
authors.lastname: Hameed
authors.affiliation: National Heart and Lung Institute, Imperial College London, London W12 0NN, UK.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Stella
authors.affiliation: National Heart and Lung Institute, Imperial College London, London W12 0NN, UK.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Bellahcene
authors.affiliation: National Heart and Lung Institute, Imperial College London, London W12 0NN, UK.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Schneider
authors.affiliation: National Heart and Lung Institute, Imperial College London, London W12 0NN, UK.
authors.forename: Sian E
authors.initials: SE
authors.lastname: Harding
authors.affiliation: The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA.|National Heart and Lung Institute, Imperial College London, London W12 0NN, UK.
authors.forename: Nadia
authors.initials: N
authors.lastname: Rosenthal
authors.affiliation: National Heart and Lung Institute, Imperial College London, London W12 0NN, UK s.sattler@imperial.ac.uk.
authors.forename: Susanne
authors.identifier: 0000-0001-9932-4109
authors.initials: S
authors.lastname: Sattler
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects; D019264:Adoptive Transfer; D000818:Animals; D001323:Autoantibodies / Q000097:blood; D015551:Autoimmunity / Q000187:drug effects*; D002311:Cardiomyopathy, Dilated / Q000139:chemically induced* / Q000150:complications / Q000276:immunology / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D014644:Genetic Variation; D006334:Heart Function Tests; D007093:Imidazoles / Q000009:adverse effects*; D007111:Immunity, Cellular / Q000187:drug effects; D007249:Inflammation / Q000473:pathology; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology; D008297:Male; D009154:Mutation / Q000235:genetics; D009205:Myocarditis / Q000139:chemically induced* / Q000150:complications / Q000276:immunology / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology; D013154:Spleen / Q000473:pathology; D051199:Toll-Like Receptor 7 / Q000819:agonists* / Q000378:metabolism; D051200:Toll-Like Receptor 8 / Q000819:agonists* / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D007093:Imidazoles; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; C402365:resiquimod
keywords: Autoimmunity; Dilated cardiomyopathy; Heart disease; Model; Myocarditis; Resiquimod; Toll-like receptor 7/8