| First Author | Liu L | Year | 2017 |
| Journal | Biochem Biophys Res Commun | Volume | 492 |
| Issue | 3 | Pages | 453-460 |
| PubMed ID | 28837808 | Mgi Jnum | J:251356 |
| Mgi Id | MGI:6103206 | Doi | 10.1016/j.bbrc.2017.08.075 |
| Citation | Liu L, et al. (2017) Elevated expression of microRNA-873 facilitates Th17 differentiation by targeting forkhead box O1 (Foxo1) in the pathogenesis of systemic lupus erythematosus. Biochem Biophys Res Commun 492(3):453-460 |
| abstractText | Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, and its pathogenesis remains mostly unknown. MicroRNAs (miRs) has drawn much attention as a crucial regulator of autoimmune diseases. In this study, we demonstrated that miR-873 expression was significantly up-regulated in patients with SLE, and its expression was positively associated with the disease severity. CD4(+) T cells, especially the Th17 subset, were found to be the major source of miR-873 expression. Using gain- and loss-of-function approaches, we further showed that miR-873 could facilitate the differentiation of CD4(+) T cells into Th17 lineage. Moreover, forkhead box O1 (Foxo1), one member of the Foxo family, was identified as a novel target gene of miR-873, and Foxo1 has been known as an inhibitor of Th17 cell differentiation. Foxo1 was observed to be markedly decreased in PBMC of patients with SLE. Notably, in vivo lentivirus-mediated inhibition of miR-873 significantly alleviated the disease severity of spontaneous SLE in MRL/lpr mice, with down-regulated levels of autoantibodies, proteinuria, and IL-17A. Our data reveal a novel mechanism in which the elevated miR-873 in PBMC of SLE promotes Th17 cell differentiation through down-regulation of Foxo1. In vivo blockade of miR-873 may serve as a novel therapeutic approach in the treatment of SLE. |
