Two types of monocytes， Ly6C and Ly6C， 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 and Ly6C 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 monocyte-derived macrophages (MDMs) and simultaneously prevents Ly6C monocyte-to-macrophage differentiation. We demonstrated an inverse clinical correlation between heart IL-17A levels and efferocytic receptor expressions in humans with heart failure (... More
Two types of monocytes， Ly6C and Ly6C， 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 and Ly6C 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 monocyte-derived macrophages (MDMs) and simultaneously prevents Ly6C 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， Ly6C MDMs act as robust phagocytes and are less pro-inflammatory， whereas Ly6C monocytes resume their differentiation into MHCII macrophages. We propose that MHCIILy6C MDMs are associated with the reduction of cardiac fibrosis and prevention of the myocarditis sequalae.
