Sustained expression of pre-TCR induced β-catenin in post-β-selection thymocytes blocks T cell development

Mai Xu, Archna Sharma, M. Zulfiquer Hossain, David L. Wiest, Jyoti Misra Sen

Research output: Contribution to journalArticlepeer-review

Abstract

Pre-TCR and IL-7R signals regulate β-selection of thymocytes and then must be down-regulated for further development. However, the molecular events that control down-regulation remain unknown. We and others have previously shown that β-catenin in cooperation with TCF regulates β-selection. In this paper, we demonstrate that β-catenin expression is stringently regulated by intrathymic signals, it is expressed at the highest levels in the pre-TCR signaled thymocytes, and is down-regulated in post-β-selection thymocytes. Pre-TCR-induced β-catenin regulates initial stages of pre-TCR signaling including expression of early growth response (Egr) genes but must be down-regulated to express RORγt, which is essential for maturation to the CD4+CD8+ double positive (DP) stage. Sustained expression of β-catenin results in the generation of IL-7R-, Egr-, and TGFβ-expressing pre-DP thymocytes that are blocked in development. These data are consistent with a model in which post-β-selection, pre-TCR-induced β-catenin expression must return to background levels for efficient transition to the DP stage.

Original languageEnglish (US)
Pages (from-to)759-765
Number of pages7
JournalJournal of Immunology
Volume182
Issue number2
StatePublished - Jan 15 2009
Externally publishedYes

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

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