Absence of nonhematopoietic MHC class II expression protects mice from experimental autoimmune myocarditis.

Details

Serval ID
serval:BIB_4200DDF12A73
Type
Article: article from journal or magazin.
Collection
Publications
Title
Absence of nonhematopoietic MHC class II expression protects mice from experimental autoimmune myocarditis.
Journal
European Journal of Immunology
Author(s)
Thelemann C., Haller S., Blyszczuk P., Kania G., Rosa M., Eriksson U., Rotman S., Reith W., Acha-Orbea H.
ISSN
1521-4141 (Electronic)
ISSN-L
0014-2980
Publication state
Published
Issued date
2016
Peer-reviewed
Oui
Volume
46
Number
3
Pages
656-664
Language
english
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 class II transactivator (CIITA) transgenic (Tg) mice) by immunization with α-myosin heavy chain peptide 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-γ, which is the major driver of nonhematopoietic MHCII expression. Mechanistically, IFN-γ 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-γ to induce endothelial MHCII expression in the heart and to progress cardiac pathology during myocarditis.
Keywords
CD4(+) T cells, Experimental autoimmune myocarditis (EAM), Endothelial antigen presentation, Interferon-gamma, MHC class II
Pubmed
Web of science
Open Access
Yes
Create date
15/04/2016 17:53
Last modification date
20/08/2019 14:43
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