IRF7-dependent IFN-β production in response to RANKL promotes medullary thymic epithelial cell development.

ABSTRACT: The contributions of IFN regulatory factor (IRF) 3/7 and the type I IFNs IFN-α/β 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-α/β 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-κB (RANK) ligand stimulation results in IFN-β upregulation, which in turn inhibits RANK signaling and facilitates AIRE expression in mTECs. Finally, we find that IRF7 is required for thymic IFN-β induction,

SUBMITTER: Otero DC 

PROVIDER: S-EPMC3608802 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature