Fig. 5.

Three phases of immune response to cardiac injury repair. This diagram shows the inflammation, proliferation, and maturation phases after cardiac injury. In the Inflammatory phase, cTMs phagocytose dying cardiomyocytes. B cells secrete immunoregulatory factors to reduce cardiac contractility and promote cardiomyocyte apoptosis. DCs mediate the recruitment of inflammatory cells such as monocytes and M1 macrophages and homeostasis. In the proliferation phase, cTMs promote the proliferation of myocardial cells and angiogenesis. Neutrophils, monocytes and M2 macrophages also promote angiogenesis though VEGF, and M1 macrophages promote tissue fibrosis and myocardial remodeling by inducing extracellular matrix release from cardiac fibroblasts. NK cells protect against cardiac fibrosis by directly restricting collagen formation of cardiac fibroblasts and preventing the accumulation of specific inflammatory populations, and NK cells also promote blood vessel remodeling. Treg cells inhibit inflammation and fibrosis and promote precursor cell proliferation and macrophage polarization. In the maturation phase, the recruitment of inflammatory cells such as macrophages, neutrophils and eosinophils is inhibited, anti-inflammatory cytokines are secreted, infiltrating immune cells regulate inflammation inactivation/reduction by mediating the fibrotic response, and inflammation and scar formation are resolved. During this phase, hepcidin inhibits macrophage-induced cardiac repair and regeneration