title: GM-CSF promotes inflammatory dendritic cell formation but does not contribute to disease progression in experimental autoimmune myocarditis.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Zürich, CH-8057 Zürich, Switzerland.
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Blyszczuk
authors.forename: Silvia
authors.initials: S
authors.lastname: Behnke
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Lüscher
authors.forename: Urs
authors.initials: U
authors.lastname: Eriksson
authors.forename: Gabriela
authors.initials: G
authors.lastname: Kania
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000276:immunology / Q000473:pathology*; D015415:Biomarkers / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology* / Q000637:transplantation; D004195:Disease Models, Animal; D018450:Disease Progression; D015870:Gene Expression / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology* / Q000494:pharmacology; D007114:Immunization; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000276:immunology / Q000473:pathology; D009205:Myocarditis / Q000139:chemically induced / Q000276:immunology / Q000473:pathology*; D009206:Myocardium / Q000276:immunology / Q000473:pathology*; D009218:Myosins; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D009218:Myosins