The Cardiac Microenvironment Instructs Divergent Monocyte Fates and Functions in Myocarditis.
Abstract
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.
Authors: | Hou X, Chen G, Bracamonte-Baran W, Choi HS, Diny NL, Sung J, Hughes D, Won T, Wood MK, Talor MV, Hackam DJ, Klingel K, Davogustto G, Taegtmeyer H, Coppens I, Barin JG, Cihakova D |
---|---|
Journal: | Cell Rep. 2019 Jul 2;28(1):172-189.e7. doi: 10.1016/j.celrep.2019.06.007. |
Year: | 2019 |
PubMed: | PMID: 31269438 (Go to PubMed) |