A novel method to identify Post-Aire stages of medullary thymic epithelial cell differentiation.
Eur J Immunol
; 51(2): 311-318, 2021 02.
Article
en En
| MEDLINE
| ID: mdl-32845012
ABSTRACT
Autoimmune regulator+ (Aire) medullary thymic epithelial cells (mTECs) play a critical role in tolerance induction. Several studies demonstrated that Aire+ mTECs differentiate further into Post-Aire cells. Yet, the identification of terminal stages of mTEC maturation depends on unique fate-mapping mouse models. Herein, we resolve this limitation by segmenting the mTEChi (MHCIIhi CD80hi ) compartment into mTECA/hi (CD24- Sca1- ), mTECB/hi (CD24+ Sca1- ), and mTECC/hi (CD24+ Sca1+ ). While mTECA/hi included mostly Aire-expressing cells, mTECB/hi contained Aire+ and Aire- cells and mTECC/hi were mainly composed of cells lacking Aire. The differential expression pattern of Aire led us to investigate the precursor-product relationship between these subsets. Strikingly, transcriptomic analysis of mTECA/hi , mTECB/hi , and mTECC/hi sequentially mirrored the specific genetic program of Early-, Late- and Post-Aire mTECs. Corroborating their Post-Aire nature, mTECC/hi downregulated the expression of tissue-restricted antigens, acquired traits of differentiated keratinocytes, and were absent in Aire-deficient mice. Collectively, our findings reveal a new and simple blueprint to survey late stages of mTEC differentiation.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Timo
/
Factores de Transcripción
/
Queratinocitos
/
Diferenciación Celular
/
Células Epiteliales
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Eur J Immunol
Año:
2021
Tipo del documento:
Article
País de afiliación:
Portugal