Beta-catenin/Tcf determines the outcome of thymic selection in response to alphabetaTCR signaling.
J Immunol
; 183(6): 3873-84, 2009 Sep 15.
Article
en En
| MEDLINE
| ID: mdl-19717519
ABSTRACT
Thymic maturation of T cells depends on the intracellular interpretation of alphabetaTCR signals by processes that are poorly understood. In this study, we report that beta-catenin/Tcf signaling was activated in double-positive thymocytes in response to alphabetaTCR engagement and impacted thymocyte selection. TCR engagement combined with activation of beta-catenin signaled thymocyte deletion, whereas Tcf-1 deficiency rescued from negative selection. Survival/apoptotis mediators including Bim, Bcl-2, and Bcl-x(L) were alternatively influenced by stabilization of beta-catenin or ablation of Tcf-1, and Bim-mediated beta-catenin induced thymocyte deletion. TCR activation in double-positive cells with stabilized beta-catenin triggered signaling associated with negative selection, including sustained overactivation of Lat and Jnk and a transient activation of Erk. These observations are consistent with beta-catenin/Tcf signaling acting as a switch that determines the outcome of thymic selection downstream the alphabetaTCR cascade.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Timo
/
Transducción de Señal
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Receptores de Antígenos de Linfocitos T alfa-beta
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Beta Catenina
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Factor 1 de Transcripción de Linfocitos T
Límite:
Animals
Idioma:
En
Revista:
J Immunol
Año:
2009
Tipo del documento:
Article
País de afiliación:
Estados Unidos