TY - JOUR
T1 - β-catenin/Tcf determines the outcome of thymic selection in response to αβTCR signaling
AU - Kovalovsky, Damian
AU - Yu, Yu
AU - Dose, Marei
AU - Emmanouilidou, Anastasia
AU - Konstantinou, Tassos
AU - Germar, Kristine
AU - Aghajani, Katayoun
AU - Guo, Zhuyan
AU - Mandal, Malay
AU - Gounari, Fotini
PY - 2009/9/15
Y1 - 2009/9/15
N2 - Thymic maturation of T cells depends on the intracellular interpretation of αβTCR signals by processes that are poorly understood. In this study, we report that β-catenin/Tcf signaling was activated in double-positive thymocytes in response to αβTCR engagement and impacted thymocyte selection. TCR engagement combined with activation of β-catenin signaled thymocyte deletion, whereas Tcf-1 deficiency rescued from negative selection. Survival/apoptotis mediators including Bim, Bcl-2, and Bcl-xL were alternatively influenced by stabilization of β-catenin or ablation of Tcf-1, and Bim-mediated β-catenin induced thymocyte deletion. TCR activation in double-positive cells with stabilized β-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 β-catenin/Tcf signaling acting as a switch that determines the outcome of thymic selection downstream the αβTCR cascade.
AB - Thymic maturation of T cells depends on the intracellular interpretation of αβTCR signals by processes that are poorly understood. In this study, we report that β-catenin/Tcf signaling was activated in double-positive thymocytes in response to αβTCR engagement and impacted thymocyte selection. TCR engagement combined with activation of β-catenin signaled thymocyte deletion, whereas Tcf-1 deficiency rescued from negative selection. Survival/apoptotis mediators including Bim, Bcl-2, and Bcl-xL were alternatively influenced by stabilization of β-catenin or ablation of Tcf-1, and Bim-mediated β-catenin induced thymocyte deletion. TCR activation in double-positive cells with stabilized β-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 β-catenin/Tcf signaling acting as a switch that determines the outcome of thymic selection downstream the αβTCR cascade.
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U2 - 10.4049/jimmunol.0901369
DO - 10.4049/jimmunol.0901369
M3 - Article
C2 - 19717519
AN - SCOPUS:70349339369
SN - 0022-1767
VL - 183
SP - 3873
EP - 3884
JO - Journal of Immunology
JF - Journal of Immunology
IS - 6
ER -