[PDF][PDF] The cardiac microenvironment instructs divergent monocyte fates and functions in myocarditis
Cell reports, 2019•cell.com
Two types of monocytes, Ly6C hi and Ly6C lo, infiltrate the heart in murine experimental
autoimmune myocarditis (EAM). We discovered a role for cardiac fibroblasts in facilitating
monocyte-to-macrophage differentiation of both Ly6C hi and Ly6C lo cells, allowing these
macrophages to perform divergent functions in myocarditis progression. During the acute
phase of EAM, IL-17A is highly abundant. It signals through cardiac fibroblasts to attenuate
efferocytosis of Ly6C hi monocyte-derived macrophages (MDMs) and simultaneously …
autoimmune myocarditis (EAM). We discovered a role for cardiac fibroblasts in facilitating
monocyte-to-macrophage differentiation of both Ly6C hi and Ly6C lo cells, allowing these
macrophages to perform divergent functions in myocarditis progression. During the acute
phase of EAM, IL-17A is highly abundant. It signals through cardiac fibroblasts to attenuate
efferocytosis of Ly6C hi monocyte-derived macrophages (MDMs) and simultaneously …
Summary
Two types of monocytes, Ly6Chi and Ly6Clo, infiltrate the heart in murine experimental autoimmune myocarditis (EAM). We discovered a role for cardiac fibroblasts in facilitating monocyte-to-macrophage differentiation of both Ly6Chi and Ly6Clo cells, allowing these macrophages to perform divergent functions in myocarditis progression. During the acute phase of EAM, IL-17A is highly abundant. It signals through cardiac fibroblasts to attenuate efferocytosis of Ly6Chi monocyte-derived macrophages (MDMs) and simultaneously prevents Ly6Clo monocyte-to-macrophage differentiation. We demonstrated an inverse clinical correlation between heart IL-17A levels and efferocytic receptor expressions in humans with heart failure (HF). In the absence of IL-17A signaling, Ly6Chi MDMs act as robust phagocytes and are less pro-inflammatory, whereas Ly6Clo monocytes resume their differentiation into MHCII+ macrophages. We propose that MHCII+Ly6Clo MDMs are associated with the reduction of cardiac fibrosis and prevention of the myocarditis sequalae.
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