Differential Features of AIRE-Induced and AIRE-Independent Promiscuous Gene Expression in Thymic Epithelial Cells.
J Immunol
; 195(2): 498-506, 2015 Jul 15.
Article
em En
| MEDLINE
| ID: mdl-26034170
ABSTRACT
Establishment of self-tolerance in the thymus depends on promiscuous expression of tissue-restricted Ags (TRA) by thymic epithelial cells (TEC). This promiscuous gene expression (pGE) is regulated in part by the autoimmune regulator (AIRE). To evaluate the commonalities and discrepancies between AIRE-dependent and -independent pGE, we analyzed the transcriptome of the three main TEC subsets in wild-type and Aire knockout mice. We found that the impact of AIRE-dependent pGE is not limited to generation of TRA. AIRE decreases, via non-cell autonomous mechanisms, the expression of genes coding for positive regulators of cell proliferation, and it thereby reduces the number of cortical TEC. In mature medullary TEC, AIRE-driven pGE upregulates non-TRA coding genes that enhance cell-cell interactions (e.g., claudins, integrins, and selectins) and are probably of prime relevance to tolerance induction. We also found that AIRE-dependent and -independent TRA present several distinctive features. In particular, relative to AIRE-induced TRA, AIRE-independent TRA are more numerous and show greater splicing complexity. Furthermore, we report that AIRE-dependent versus -independent TRA project nonredundant representations of peripheral tissues in the thymus.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Timo
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Fatores de Transcrição
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Tolerância a Antígenos Próprios
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Células Epiteliais
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Transcriptoma
Limite:
Animals
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article