β-catenin/Tcf determines the outcome of thymic selection in response to αβTCR signaling

Damian Kovalovsky, Yu Yu, Marei Dose, Anastasia Emmanouilidou, Tassos Konstantinou, Kristine Germar, Katayoun Aghajani, Zhuyan Guo, Malay Mandal, Fotini Gounari

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3873-3884
Number of pages12
JournalJournal of Immunology
Volume183
Issue number6
DOIs
StatePublished - Sep 15 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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