edoc

CD11b+ monocytes abrogate Th17 CD4+ T cell-mediated experimental autoimmune myocarditis

Valaperti, A. and Marty, R. R. and Kania, G. and Germano, D. and Mauermann, N. and Dirnhofer, S. and Leimenstoll, B. and Blyszczuk, P. and Dong, C. and Mueller, C. and Hunziker, L. and Eriksson, U.. (2008) CD11b+ monocytes abrogate Th17 CD4+ T cell-mediated experimental autoimmune myocarditis. Journal of immunology, Vol. 180, H. 4. pp. 2686-2695.

Full text not available from this repository.

Official URL: http://edoc.unibas.ch/dok/A6007191

Downloads: Statistics Overview

Abstract

Experimental autoimmune myocarditis (EAM) represents a Th17 T cell-mediated mouse model of postinflammatory heart disease. In BALB/c wild-type mice, EAM is a self-limiting disease, peaking 21 days after alpha-myosin H chain peptide (MyHC-alpha)/CFA immunization and largely resolving thereafter. In IFN-gammaR(-/-) mice, however, EAM is exacerbated and shows a chronic progressive disease course. We found that this progressive disease course paralleled persistently elevated IL-17 release from T cells infiltrating the hearts of IFN-gammaR(-/-) mice 30 days after immunization. In fact, IL-17 promoted the recruitment of CD11b(+) monocytes, the major heart-infiltrating cells in EAM. In turn, CD11b(+) monocytes suppressed MyHC-alpha-specific Th17 T cell responses IFN-gamma-dependently in vitro. In vivo, injection of IFN-gammaR(+/+)CD11b(+), but not IFN-gammaR(-/-)CD11b(+), monocytes, suppressed MyHC-alpha-specific T cells, and abrogated the progressive disease course in IFN-gammaR(-/-) mice. Finally, coinjection of MyHC-alpha-specific, but not OVA-transgenic, IFN-gamma-releasing CD4(+) Th1 T cell lines, together with MyHC-alpha-specific Th17 T cells protected RAG2(-/-) mice from EAM. In conclusion, CD11b(+) monocytes play a dual role in EAM: as a major cellular substrate of IL-17-induced inflammation and as mediators of an IFN-gamma-dependent negative feedback loop confining disease progression.
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Ehemalige Einheiten Medizinische Fächer (Klinik) > Stationäre innere Medizin (Schifferli)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Ehemalige Einheiten Medizinische Fächer (Klinik) > Stationäre innere Medizin (Schifferli)
03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Pneumologie > Pneumologie (Tamm)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Pneumologie > Pneumologie (Tamm)
03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Histopathologie (Dirnhofer)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Histopathologie (Dirnhofer)
UniBasel Contributors:Dirnhofer, Stephan and Müller, Christian and Eriksson, Urs and Hunziker Munsch, Lukas Christoph
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:American Assoc. of Immunologists
ISSN:0022-1767
Note:Publication type according to Uni Basel Research Database: Journal article
Related URLs:
Identification Number:
Last Modified:08 Nov 2012 16:23
Deposited On:08 Nov 2012 16:18

Repository Staff Only: item control page