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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-11960

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

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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.

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Cardiology
DDC:610 Medicine & health
Language:English
Date:15 January 2008
Deposited On:28 Jan 2009 17:51
Last Modified:27 Nov 2013 23:06
Publisher:American Association of Immunologists
ISSN:0022-1767
Free access at:PubMed ID. An embargo period may apply.
Official URL:http://www.jimmunol.org/cgi/content/abstract/180/4/2686
PubMed ID:18250481
Citations:Web of Science®. Times Cited: 64
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