| First Author | Haljasorg U | Year | 2015 |
| Journal | Eur J Immunol | Volume | 45 |
| Issue | 12 | Pages | 3246-56 |
| PubMed ID | 26364592 | Mgi Jnum | J:233730 |
| Mgi Id | MGI:5787902 | Doi | 10.1002/eji.201545928 |
| Citation | Haljasorg U, et al. (2015) A highly conserved NF-kappaB-responsive enhancer is critical for thymic expression of Aire in mice. Eur J Immunol 45(12):3246-56 |
| abstractText | Autoimmune regulator (Aire) has a unique expression pattern in thymic medullary epithelial cells (mTECs), in which it plays a critical role in the activation of tissue-specific antigens. The expression of Aire in mTECs is activated by receptor activator of nuclear factor kappaB (RANK) signaling; however, the molecular mechanism behind this activation is unknown. Here, we characterize a conserved noncoding sequence 1 (CNS1) containing two NF-kappaB binding sites upstream of the Aire coding region. We show that CNS1-deficient mice lack thymic expression of Aire and share several features of Aire-knockout mice, including downregulation of Aire-dependent genes, impaired terminal differentiation of the mTEC population, and reduced production of thymic Treg cells. In addition, we show that CNS1 is indispensable for RANK-induced Aire expression and that CNS1 is activated by NF-kappaB pathway complexes containing RelA. Together, our results indicate that CNS1 is a critical link between RANK signaling, NF-kappaB activation, and thymic expression of Aire. |
