Sequential phases in the development of Aire-expressing medullary thymic epithelial cells involve distinct cellular input

White, A. J. and Withers, D. R. and Parnell, S. M. and Scott, H. S. and Finke, D. and Lane, P. J. and Jenkinson, E. J. and Anderson, G.. (2008) Sequential phases in the development of Aire-expressing medullary thymic epithelial cells involve distinct cellular input. European Journal of Immunology, Vol. 38, H. 4. pp. 942-947.

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Official URL: http://edoc.unibas.ch/dok/A6006862

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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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Children's Hospital > Developmental Immunology (Finke)
UniBasel Contributors:Finke, Daniela
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Verl. Chemie
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:08 Nov 2012 16:23
Deposited On:08 Nov 2012 16:18

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