| First Author | Otero DC | Year | 2013 |
| Journal | J Immunol | Volume | 190 |
| Issue | 7 | Pages | 3289-98 |
| PubMed ID | 23440417 | Mgi Jnum | J:194737 |
| Mgi Id | MGI:5474683 | Doi | 10.4049/jimmunol.1203086 |
| Citation | Otero DC, et al. (2013) IRF7-Dependent IFN-beta Production in Response to RANKL Promotes Medullary Thymic Epithelial Cell Development. J Immunol 190(7):3289-98 |
| abstractText | The contributions of IFN regulatory factor (IRF) 3/7 and the type I IFNs IFN-alpha/beta to the innate host defense have been extensively investigated; however, their role in thymic development is less clear. In this study, we show that mice lacking the type I IFN receptor IFN-alpha/beta receptor (IFNAR) or the downstream transcription factor STAT1 harbor a significant reduction in self-Ag-presenting, autoimmune regulator (AIRE)(+) medullary thymic epithelial cells (mTECs). Constitutive IFNAR signaling occurs in the thymic medulla in the absence of infection or inflammation. Receptor activator for NF-kappaB (RANK) ligand stimulation results in IFN-beta upregulation, which in turn inhibits RANK signaling and facilitates AIRE expression in mTECs. Finally, we find that IRF7 is required for thymic IFN-beta induction, maintenance of thymic architecture, and mTEC differentiation. We conclude that spatially and temporally coordinated cross talks between the RANK ligand/RANK and IRF7/IFN-beta/IFNAR/STAT1 pathways are essential for differentiation of AIRE(+) mTECs. |
