Overexpression of ICAT highlights a role for catenin-mediated canonical Wnt signalling in early T cell development

Eur J Immunol. 2006 Sep;36(9):2376-83. doi: 10.1002/eji.200535721.

Abstract

Transcription factors of the T cell factor/lymphoid enhancing factor (Tcf/Lef) family are key regulators in the development of T cell precursors to the CD4+8+ stage. These factors are known targets of the canonical Wnt signalling pathway, and regulate transcription of Wnt target genes following interaction with the armadillo repeat-containing protein beta-catenin. However, as recent studies show normal thymocyte maturation in the absence of either beta-catenin or its homologue gamma-catenin, the role of Wnt signalling in Tcf/Lef activation during T cell development is controversial. To directly investigate the importance of catenin-mediated Wnt signalling in early thymocytes, we have compared the expression of beta- and gamma-catenin and analysed distinct stages of T cell precursor maturation following overexpression of inhibitor of beta-catenin and Tcf (ICAT), which inhibits Wnt signalling by preventing binding of armadillo repeat-containing proteins to Tcf/Lef. By direct retroviral gene targeting of CD4-8- and CD4+8+ precursors, we show that ICAT overexpression inhibits the CD4-8--to-CD4+8+ transition, but not the CD4+8+-to-CD4+8- or -CD4-8+ transition. Collectively, our data support a model in which canonical Wnt signalling influences T cell development in the thymus by playing an essential role in the maturation of CD4-8- but not CD4+8+ thymocytes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • CD4 Antigens / immunology
  • CD4 Antigens / metabolism
  • CD8 Antigens / immunology
  • CD8 Antigens / metabolism
  • Catenins / biosynthesis*
  • Catenins / immunology
  • Cell Cycle Proteins / immunology*
  • Cell Cycle Proteins / metabolism
  • Cell Differentiation / immunology
  • Flow Cytometry
  • Mice
  • Mice, Inbred BALB C
  • Repressor Proteins
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / immunology*
  • Stem Cells / cytology
  • Stem Cells / immunology
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology
  • Thymus Gland / cytology
  • Thymus Gland / embryology*
  • Transcription Factors / immunology*
  • Transcription Factors / metabolism
  • Wnt Proteins / immunology*
  • Wnt Proteins / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • CD4 Antigens
  • CD8 Antigens
  • Catenins
  • Cell Cycle Proteins
  • Ctnnbip1 protein, mouse
  • Repressor Proteins
  • Transcription Factors
  • Wnt Proteins