Blyszczuk P Kania G Dieterle T Marty RR Valaperti A Berthonneche C Pedrazzini T Berger CT Dirnhofer S Matter CM Penninger JM Lüscher TF Eriksson U 2009 RATIONALE The myeloid differentiation factor (MyD)88/interleukin (IL)-1 axis activates self-antigen-presenting cells and promotes autoreactive CD4(+) T-cell expansion in experimental autoimmune myocarditis, a mouse model of inflammatory heart disease. OBJECTIVE The aim of this study was to determine the role of MyD88 and IL-1 in the progression of acute myocarditis to an end-stage heart failure. METHODS AND RESULTS Using alpha-myosin heavy chain peptide (MyHC-alpha)-loaded, activated dendritic cells, we induced myocarditis in wild-type and MyD88(-/-) mice with similar distributions of heart-infiltrating cell subsets and comparable CD4(+) T-cell responses. Injection of complete Freund's adjuvant (CFA) or MyHC-alpha/CFA into diseased mice promoted cardiac fibrosis, induced ventricular dilation, and impaired heart function in wild-type but not in MyD88(-/-) mice. Experiments with chimeric mice confirmed the bone marrow origin of the fibroblasts replacing inflammatory infiltrates and showed that MyD88 and IL-1 receptor type I signaling on bone marrow-derived cells was critical for development of cardiac fibrosis during progression to heart failure. CONCLUSIONS Our findings indicate a critical role of MyD88/IL-1 signaling in the bone marrow compartment in postinflammatory cardiac fibrosis and heart failure and point to novel therapeutic strategies against inflammatory cardiomyopathy. application/pdf https://sonar.ch/global/documents/4455 eng info:eu-repo/semantics/altIdentifier/doi/10.1161/CIRCRESAHA.109.199802 info:eu-repo/semantics/altIdentifier/pmid/19762681 info:eu-repo/semantics/openAccess Circulation research. - 2009 Animals Autoimmunity Bone Marrow Transplantation CD4-Positive T-Lymphocytes Cardiomyopathy, Dilated Cells, Cultured Dendritic Cells Disease Models, Animal Disease Progression Fibroblasts Fibrosis Freund's Adjuvant Green Fluorescent Proteins Heart Failure Immunity, Innate Interleukin-1beta Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Myeloid Differentiation Factor 88 Myocarditis Myocardium Myosin Heavy Chains Phenotype Receptors, Interleukin-1 Type I Signal Transduction Transplantation Chimera Myeloid differentiation factor-88/interleukin-1 signaling controls cardiac fibrosis and heart failure progression in inflammatory dilated cardiomyopathy. http://purl.org/coar/resource_type/c_6501