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 journalArticle

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

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Catenins
Thymocytes
T-Lymphocytes
Growth
Down-Regulation
Genes

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Xu, M., Sharma, A., Hossain, M. Z., Wiest, D. L., & Sen, J. M. (2009). Sustained expression of pre-TCR induced β-catenin in post-β-selection thymocytes blocks T cell development. Journal of Immunology, 182(2), 759-765.

Sustained expression of pre-TCR induced β-catenin in post-β-selection thymocytes blocks T cell development. / Xu, Mai; Sharma, Archna; Hossain, M. Zulfiquer; Wiest, David L.; Sen, Jyoti Misra.

In: Journal of Immunology, Vol. 182, No. 2, 15.01.2009, p. 759-765.

Research output: Contribution to journalArticle

Xu, M, Sharma, A, Hossain, MZ, Wiest, DL & Sen, JM 2009, 'Sustained expression of pre-TCR induced β-catenin in post-β-selection thymocytes blocks T cell development', Journal of Immunology, vol. 182, no. 2, pp. 759-765.
Xu, Mai ; Sharma, Archna ; Hossain, M. Zulfiquer ; Wiest, David L. ; Sen, Jyoti Misra. / Sustained expression of pre-TCR induced β-catenin in post-β-selection thymocytes blocks T cell development. In: Journal of Immunology. 2009 ; Vol. 182, No. 2. pp. 759-765.
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