Ectopic Aire Expression in the Thymic Cortex Reveals Inherent Properties of Aire as a Tolerogenic Factor within the Medulla.
J Immunol
; 195(10): 4641-9, 2015 Nov 15.
Article
en En
| MEDLINE
| ID: mdl-26453754
ABSTRACT
Cortical thymic epithelial cells (cTECs) and medullary thymic epithelial cells (mTECs) play essential roles in the positive and negative selection of developing thymocytes, respectively. Aire in mTECs plays an essential role in the latter process through expression of broad arrays of tissue-restricted Ags. To determine whether the location of Aire within the medulla is absolutely essential or whether Aire could also function within the cortex for establishment of self-tolerance, we used bacterial artificial chromosome technology to establish a semiknockin strain of NOD-background (ß5t/Aire-transgenic) mice expressing Aire under control of the promoter of ß5t, a thymoproteasome expressed exclusively in the cortex. Although Aire was expressed in cTECs as typical nuclear dot protein in ß5t/Aire-Tg mice, cTECs expressing Aire ectopically did not confer transcriptional expression of either Aire-dependent or Aire-independent tissue-restricted Ag genes. We then crossed ß5t/Aire-Tg mice with Aire-deficient NOD mice, generating a strain in which Aire expression was confined to cTECs. Despite the presence of Aire(+) cTECs, these mice succumbed to autoimmunity, as did Aire-deficient NOD mice. The thymic microenvironment harboring Aire(+) cTECs, within which many Aire-activated genes were present, also showed no obvious alteration of positive selection, suggesting that Aire's unique property of generating a self-tolerant T cell repertoire is functional only in mTECs.
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Banco de datos:
MEDLINE
Asunto principal:
Timo
/
Factores de Transcripción
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Autoinmunidad
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Autotolerancia
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Timocitos
Límite:
Animals
Idioma:
En
Año:
2015
Tipo del documento:
Article