W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
Cell Rep. 2019 Jul 2;28(1):172-189.e7. doi: 10.1016/j.celrep.2019.06.007.
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.
两种类型的单核细胞，Ly6C 和 Ly6C，浸润在实验性自身免疫性心肌炎（EAM）的心脏中。我们发现心肌成纤维细胞在促进 Ly6C 和 Ly6C 细胞向巨噬细胞分化中发挥作用，使这些巨噬细胞在心肌炎进展中发挥不同的功能。在 EAM 的急性期，IL-17A 含量非常高。它通过心肌成纤维细胞发出信号，减弱 Ly6C 单核细胞来源的巨噬细胞（MDM）的吞噬作用，同时阻止 Ly6C 单核细胞向巨噬细胞分化。我们在心力衰竭（HF）患者中证明了心脏 IL-17A 水平与吞噬作用受体表达之间的临床负相关。在缺乏 IL-17A 信号的情况下，Ly6C MDM 作为强大的吞噬细胞起作用，并且炎症反应较少，而 Ly6C 单核细胞恢复其分化为 MHCII 巨噬细胞。我们提出，MHCIILy6C MDM 与减少心脏纤维化和预防心肌炎后遗症有关。
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