| First Author | Hou X | Year | 2019 |
| Journal | Cell Rep | Volume | 28 |
| Issue | 1 | Pages | 172-189.e7 |
| PubMed ID | 31269438 | Mgi Jnum | J:286927 |
| Mgi Id | MGI:6390650 | Doi | 10.1016/j.celrep.2019.06.007 |
| Citation | Hou X, et al. (2019) The Cardiac Microenvironment Instructs Divergent Monocyte Fates and Functions in Myocarditis. Cell Rep 28(1):172-189.e7 |
| abstractText | 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 prevents Ly6C(lo) 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(hi) MDMs act as robust phagocytes and are less pro-inflammatory, whereas Ly6C(lo) monocytes resume their differentiation into MHCII(+) macrophages. We propose that MHCII(+)Ly6C(lo) MDMs are associated with the reduction of cardiac fibrosis and prevention of the myocarditis sequalae. |
