AI Article Synopsis
- The MyD88/IL-1 axis is important for activating cells that present self-antigens and promoting the expansion of autoreactive CD4(+) T-cells in a mouse model of myocarditis.
- The study aimed to investigate how MyD88 and IL-1 contribute to the transition from acute myocarditis to severe heart failure.
- Results showed that MyD88 is essential for cardiac fibrosis and heart dysfunction, suggesting potential new treatment approaches for inflammatory heart diseases.
Article Abstract
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.
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| http://dx.doi.org/10.1161/CIRCRESAHA.109.199802 | DOI Listing |
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