| First Author | Wu L | Year | 2014 |
| Journal | J Exp Med | Volume | 211 |
| Issue | 7 | Pages | 1449-64 |
| PubMed ID | 24935258 | Mgi Jnum | J:214440 |
| Mgi Id | MGI:5602988 | Doi | 10.1084/jem.20132126 |
| Citation | Wu L, et al. (2014) Cardiac fibroblasts mediate IL-17A-driven inflammatory dilated cardiomyopathy. J Exp Med 211(7):1449-64 |
| abstractText | Inflammatory dilated cardiomyopathy (DCMi) is a major cause of heart failure in individuals below the age of 40. We recently reported that IL-17A is required for the development of DCMi. We show a novel pathway connecting IL-17A, cardiac fibroblasts (CFs), GM-CSF, and heart-infiltrating myeloid cells with the pathogenesis of DCMi. Il17ra(-/-) mice were protected from DCMi, and this was associated with significantly diminished neutrophil and Ly6Chi monocyte/macrophage (MO/MPhi) cardiac infiltrates. Depletion of Ly6Chi MO/MPhi also protected mice from DCMi. Mechanistically, IL-17A stimulated CFs to produce key chemokines and cytokines that are critical downstream effectors in the recruitment and differentiation of myeloid cells. Moreover, IL-17A directs Ly6Chi MO/MPhi in trans toward a more proinflammatory phenotype via CF-derived GM-CSF. Collectively, this IL-17A-fibroblast-GM-CSF-MO/MPhi axis could provide a novel target for the treatment of DCMi and related inflammatory cardiac diseases. |
