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Systemic autoimmunity induced by Toll-like receptor 7/8 agonist Resiquimod causes myocarditis and dilated cardiomyopathy: a new model of autoimmune heart disease

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Title: Systemic autoimmunity induced by Toll-like receptor 7/8 agonist Resiquimod causes myocarditis and dilated cardiomyopathy: a new model of autoimmune heart disease
Authors: Hasham, MG
Baxan, N
Stuckey, D
Dent, O
Branca, J
Perkins, BRA
Duffy, T
Hameed, TS
Stella, SE
Bellahcene, M
Schneider, MD
Harding, SE
Rosenthal, N
Sattler, S
Item Type: Journal Article
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 characterize immune-mediated cardiac tissue damage in a new model of SLE induced by topical application of the TLR-7/8 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.
Issue Date: 1-Mar-2017
Date of Acceptance: 18-Jan-2017
URI: http://hdl.handle.net/10044/1/44151
DOI: https://dx.doi.org/10.1242/dmm.027409
ISSN: 1754-8411
Publisher: Company of Biologists
Start Page: 259
End Page: 270
Journal / Book Title: Disease Models & Mechanisms
Volume: 10
Copyright Statement: © 2017. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
Sponsor/Funder: British Heart Foundation
Wellcome Trust
Medical Research Council (MRC)
British Heart Foundation
Funder's Grant Number: RM/13/1/30157
105603/Z/14/Z
MR/L022699/1
PG/16/93/32345
Keywords: Science & Technology
Life Sciences & Biomedicine
Cell Biology
Pathology
Autoimmunity
Dilated cardiomyopathy
Heart disease
Myocarditis
Model
Resiquimod
Toll-like receptor 7/8
LUPUS-ERYTHEMATOSUS
CARDIAC INVOLVEMENT
B-CELLS
RHEUMATOID-ARTHRITIS
T-CELLS
AUTOANTIBODIES
MICE
PATHOGENESIS
DERMATOMYOSITIS
POLYMYOSITIS
Developmental Biology
06 Biological Sciences
11 Medical And Health Sciences
Publication Status: Published
Article Number: DMM/2016/027409
Appears in Collections:Department of Medicine (up to 2019)



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