| First Author | Liu SQ | Year | 2014 |
| Journal | J Biol Chem | Volume | 289 |
| Issue | 18 | Pages | 12446-56 |
| PubMed ID | 24644282 | Mgi Jnum | J:213175 |
| Mgi Id | MGI:5583002 | Doi | 10.1074/jbc.M114.550723 |
| Citation | Liu SQ, et al. (2014) miR-17-92 cluster targets phosphatase and tensin homology and Ikaros Family Zinc Finger 4 to promote TH17-mediated inflammation. J Biol Chem 289(18):12446-56 |
| abstractText | The miR-17-92 cluster regulates a broad spectrum of biological processes of T cell immunity. This cluster was found to facilitate T cell proliferation, enhance antitumor activities and promote T cell-dependent antibody responses. However, little is known about the role of this miRNA cluster in the development of autoimmune diseases. Multiple sclerosis is a neuro-destructive autoimmune disease caused by the pathogenicity of TH17 cells, whose differentiation is tightly controlled by a variety of transcriptional and post-transcriptional regulators. Our study unveils the critical role of miR-17-92 in TH17 differentiation: T cell-specific miR-17-92 deficiency reduced TH17 differentiation and ameliorated experimental autoimmune encephalomyelitis (EAE) symptoms. We demonstrated that miR-17 and miR-19b are the two miRNAs in this cluster responsible for promoting TH17 responses. MiR-19b represses the expression of Phosphatase and Tensin Homology (PTEN), thereby augmenting the PI3K-AKT-mTOR axis essential for proper TH17 differentiation. Meanwhile, miR-17 enhances TH17 polarization by inhibiting a novel target, Ikaros Family Zinc Finger 4 (IKZF4). By establishing the miR-17-92 cluster as a key driver of TH17 responses, our data identify this miRNA cluster as a potential therapeutic target for the clinical intervention of multiple sclerosis. |
