| First Author | White AJ | Year | 2008 |
| Journal | Eur J Immunol | Volume | 38 |
| Issue | 4 | Pages | 942-7 |
| PubMed ID | 18350550 | Mgi Jnum | J:133775 |
| Mgi Id | MGI:3784130 | Doi | 10.1002/eji.200738052 |
| Citation | White AJ, et al. (2008) Sequential phases in the development of Aire-expressing medullary thymic epithelial cells involve distinct cellular input. Eur J Immunol 38(4):942-7 |
| abstractText | Intrathymic deletion of immature thymocytes that express self-reactive TCR specificities is essential in the generation of self tolerance. Medullary thymic epithelial cells (mTEC) expressing the transcriptional regulator Aire play a key role in this process by regulating expression of tissue-restricted antigens to ensure tolerance to peripheral tissues. Here, we have analysed the cellular and molecular requirements for the initial appearance of Aire(+) mTEC in the embryonic thymus, in addition to their persistence in the adult thymus. Analysis of thymic ontogeny shows that the emergence of embryonic Aire(+) mTEC occurs prior to the appearance of mature thymocytes, and depends upon lymphoid tissue inducer cells expressing retinoic acid receptor-related orphan receptor gamma. In the adult thymus, we show that Aire(+) mTEC develop in the absence of thymocyte positive and negative selection and CD40 signalling, but are present at reduced frequency. Collectively these data support a model where the initial differentiation of Aire(+) mTEC involves receptor activator of NF-kappaB (RANK)-RANKL interactions with lymphoid tissue inducer cells, with subsequent mTEC turnover and/or survival involving CD40-mediated signalling following interactions with mature CD4(+) thymocytes that express CD40L. |
