Citation

Granulocyte macrophage-colony stimulating factor (GM-CSF) is critically required for the induction of experimental autoimmune myocarditis (EAM), a model of post-inflammatory dilated cardiomyopathy. Its specific role in the progression of myocarditis into end stage heart failure is not known.,BALB/c mice were immunized with myosin peptide and complete Freund’s adjuvant at days 0 and 7. Heart-infiltrating inflammatory CD133(+) progenitors were isolated from inflamed hearts at the peak of inflammation (day 21). In the presence of GM-CSF, inflammatory CD133(+) progenitors up-regulated integrin, alpha X (CD11c), class II major histocompatibility complex, CD80 and CD86 co-stimulatory molecules reflecting an inflammatory dendritic cell (DC) phenotype. Inflammatory DCs stimulated antigen-specific CD4(+) T cell proliferation and induced myocarditis after myosin peptide loading and adoptive transfer in healthy mice. Moreover, GM-CSF treatment of mice after the peak of disease, between days 21 and 29 of EAM, transiently increased accumulation of inflammatory DCs in the myocardium. Importantly, bone marrow-derived CD11b(+) monocytes, rather than inflammatory CD133(+) progenitors represent the dominant cellular source of heart-infiltrating inflammatory DCs in EAM. In contrast, GM-CSF treatment neither affected numbers of heart-infiltrating CD45(+) and CD3(+) T cells nor the development of post-inflammatory fibrosis.,GM-CSF treatment promotes formation of inflammatory DCs in EAM. In contrast to the active roles of GM-CSF and DCs in EAM induction, GM-CSF-induced inflammatory DCs neither prevent resolution of active inflammation, nor contribute to post-inflammatory cardiac remodelling. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Cardiac Pathways of Differentiation, Metabolism and Contraction.