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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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|
|Date:||15 January 2008|
|Deposited On:||28 Jan 2009 17:51|
|Last Modified:||23 Nov 2012 17:26|
|Publisher:||American Association of Immunologists|
|Free access at:||PubMed ID. An embargo period may apply.|
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