1. Absence of nonhematopoietic MHC class II expression protects mice from experimental autoimmune myocarditis
- Author
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Thelemann C Haller S Blyszczuk P Kania G Rosa M Eriksson U Rotman S Reith W Acha-Orbea H.
- Subjects
chemical and pharmacologic phenomena ,respiratory system - Abstract
Experimental Autoimmune Myocarditis (EAM) is a CD4+ T cell mediated model of human inflammatory dilated cardiomyopathies. Heart specific CD4+ T cell activation is dependent on autoantigens presented by MHC class II (MHCII) molecules expressed on professional APCs. In this study we addressed the role of inflammation induced MHCII expression by cardiac nonhematopoietic cells on EAM development. EAM was induced in susceptible mice lacking inducible expression of MHCII molecules on all nonhematopoietic cells (pIV / K14 CIITA Tg mice) by immunization with a myosin heavy chain peptide (a MyHC) in CFA. Lack of inducible nonhematopoietic MHCII expression in pIV / K14 CIITA Tg mice conferred EAM resistance. In contrast cardiac pathology was induced in WT and heterozygous mice and correlated with elevated cardiac endothelial MHCII expression. Control mice with myocarditis displayed an increase in infiltrating CD4+ T cells and in expression of IFN ? which is the major driver of nonhematopoietic MHCII expression. Mechanistically IFN ? neutralization in WT mice shortly before disease onset resulted in reduced cardiac MHCII expression and pathology. These findings reveal a previously overlooked contribution of IFN ? to induce endothelial MHCII expression in the heart and to progress cardiac pathology during myocarditis. This article is protected by copyright. All rights reserved.
- Published
- 2016