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https://hdl.handle.net/2440/52547
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dc.contributor.author | White, A. | - |
dc.contributor.author | Withers, D. | - |
dc.contributor.author | Parnell, S. | - |
dc.contributor.author | Scott, H. | - |
dc.contributor.author | Finke, D. | - |
dc.contributor.author | Lane, P. | - |
dc.contributor.author | Jenkinson, E. | - |
dc.contributor.author | Anderson, G. | - |
dc.date.issued | 2008 | - |
dc.identifier.citation | European Journal of Immunology, 2008; 38(4):942-947 | - |
dc.identifier.issn | 0014-2980 | - |
dc.identifier.issn | 1521-4141 | - |
dc.identifier.uri | http://hdl.handle.net/2440/52547 | - |
dc.description.abstract | 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. | - |
dc.description.statementofresponsibility | Andrea J. White, David R. Withers, Sonia M. Parnell, Hamish S. Scott, Daniela Finke, Peter J. L. Lane, Eric J. Jenkinson and Graham Anderson | - |
dc.language.iso | en | - |
dc.publisher | Wiley-V C H Verlag GMBH | - |
dc.source.uri | http://dx.doi.org/10.1002/eji.200738052 | - |
dc.subject | Cell differentiation | - |
dc.subject | Lymphoid organs | - |
dc.subject | Thymus | - |
dc.title | Sequential phases in the development of Aire-expressing medullary thymic epithelial cells involve distinct cellular input | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1002/eji.200738052 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Scott, H. [0000-0002-5813-631X] | - |
Appears in Collections: | Aurora harvest 5 Medicine publications |
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