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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Published version
Author(s)
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.
Date Issued
2017-03-01
Date Acceptance
2017-01-18
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.
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
British Heart Foundation
Wellcome Trust
Medical Research Council (MRC)
British Heart Foundation
Grant Number
RM/13/1/30157
105603/Z/14/Z
MR/L022699/1
PG/16/93/32345
Subjects
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