| First Author | Ramirez-Ortiz ZG | Year | 2015 |
| Journal | Nat Immunol | Volume | 16 |
| Issue | 5 | Pages | 495-504 |
| PubMed ID | 25848864 | Mgi Jnum | J:231858 |
| Mgi Id | MGI:5775261 | Doi | 10.1038/ni.3143 |
| Citation | Ramirez-Ortiz ZG, et al. (2015) The receptor TREML4 amplifies TLR7-mediated signaling during antiviral responses and autoimmunity. Nat Immunol 16(5):495-504 |
| abstractText | The molecules and pathways that fine-tune innate inflammatory responses mediated by Toll-like receptor 7 (TLR7) remain to be fully elucidated. Using an unbiased genome-scale screen with short hairpin RNA (shRNA), we identified the receptor TREML4 as an essential positive regulator of TLR7 signaling. Macrophages from Treml4(-/-) mice were hyporesponsive to TLR7 agonists and failed to produce type I interferons due to impaired phosphorylation of the transcription factor STAT1 by the mitogen-activated protein kinase p38 and decreased recruitment of the adaptor MyD88 to TLR7. TREML4 deficiency reduced the production of inflammatory cytokines and autoantibodies in MRL/lpr mice, which are prone to systemic lupus erythematosus (SLE), and inhibited the antiviral immune response to influenza virus. Our data identify TREML4 as a positive regulator of TLR7 signaling and provide insight into the molecular mechanisms that control antiviral immunity and the development of autoimmunity. |
