Innate signaling promotes formation of regulatory nitric oxide-producing dendritic cells limiting T-cell expansion in experimental autoimmune myocarditis.

Détails

ID Serval
serval:BIB_329A4BA438F1
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Innate signaling promotes formation of regulatory nitric oxide-producing dendritic cells limiting T-cell expansion in experimental autoimmune myocarditis.
Périodique
Circulation
Auteur(s)
Kania G., Siegert S., Behnke S., Prados-Rosales R., Casadevall A., Lüscher T.F., Luther S.A., Kopf M., Eriksson U., Blyszczuk P.
ISSN
1524-4539 (Electronic)
ISSN-L
0009-7322
Statut éditorial
Publié
Date de publication
2013
Volume
127
Numéro
23
Pages
2285-2294
Langue
anglais
Résumé
BACKGROUND: Activation of innate pattern-recognition receptors promotes CD4+ T-cell-mediated autoimmune myocarditis and subsequent inflammatory cardiomyopathy. Mechanisms that counterregulate exaggerated heart-specific autoimmunity are poorly understood.
METHODS AND RESULTS: Experimental autoimmune myocarditis was induced in BALB/c mice by immunization with α-myosin heavy chain peptide and complete Freund's adjuvant. Together with interferon-γ, heat-killed Mycobacterium tuberculosis, an essential component of complete Freund's adjuvant, converted CD11b(hi)CD11c(-) monocytes into tumor necrosis factor-α- and nitric oxide synthase 2-producing dendritic cells (TipDCs). Heat-killed M. tuberculosis stimulated production of nitric oxide synthase 2 via Toll-like receptor 2-mediated nuclear factor-κB activation. TipDCs limited antigen-specific T-cell expansion through nitric oxide synthase 2-dependent nitric oxide production. Moreover, they promoted nitric oxide synthase 2 production in hematopoietic and stromal cells in a paracrine manner. Consequently, nitric oxide synthase 2 production by both radiosensitive hematopoietic and radioresistant stromal cells prevented exacerbation of autoimmune myocarditis in vivo.
CONCLUSIONS: Innate Toll-like receptor 2 stimulation promotes formation of regulatory TipDCs, which confine autoreactive T-cell responses in experimental autoimmune myocarditis via nitric oxide. Therefore, activation of innate pattern-recognition receptors is critical not only for disease induction but also for counterregulatory mechanisms, protecting the heart from exaggerated autoimmunity.
Mots-clé
autoimmunity, immunology, myocarditis, nitric oxide
Pubmed
Web of science
Open Access
Oui
Création de la notice
14/08/2013 9:46
Dernière modification de la notice
20/08/2019 14:18
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