LEF-1 negatively controls interleukin-4 expression through a proximal promoter regulatory element

J Biol Chem. 2008 Aug 15;283(33):22490-7. doi: 10.1074/jbc.M804096200. Epub 2008 Jun 25.


Lymphoid enhancer-binding factor 1 (LEF-1) and T cell factor (TCF-1) are downstream effectors of the Wnt signaling pathway and are involved in the regulation of T cell development in the thymus. LEF-1 and TCF-1 are also expressed in mature peripheral primary T cells, but their expression is down-regulated following T cell activation. Although the decisive roles of LEF-1 and TCF-1 in the early stages of T cell development are well documented, the functions of these factors in mature peripheral T cells are largely unknown. Recently, LEF-1 was shown to suppress Th2 cytokines interleukin-4 (IL-4), -5, and -13 expression from the developing Th2 cells that overexpress LEF-1 through retrovirus gene transduction. In this study, we further investigated the expression and functions of LEF-1 and TCF-1 in peripheral CD4+ T cells and revealed that LEF-1 is dominantly expressed in Th1 but not in Th2 cells. We identified a high affinity LEF-1-binding site in the negative regulatory element of the IL-4 promoter. Knockdown LEF-1 expression by LEF-1-specific small interfering RNA resulted in an increase in the IL-4 mRNA expression. This study further confirms a negative regulatory role of LEF-1 in mature peripheral T cells. Furthermore, we found that IL-4 stimulation possesses a negative effect on the expressions of LEF-1 and TCF-1 in primary T cells, suggesting a positive feedback effect of IL-4 on IL4 gene expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / physiology
  • Cell Differentiation
  • Cell Line, Tumor
  • Gene Expression Regulation
  • Humans
  • Interleukin-4 / genetics*
  • Interleukin-4 / metabolism
  • Leukemia, T-Cell
  • Lymphoid Enhancer-Binding Factor 1 / genetics
  • Lymphoid Enhancer-Binding Factor 1 / metabolism*
  • Mice
  • Promoter Regions, Genetic*
  • Regulatory Sequences, Ribonucleic Acid / genetics*


  • Lef1 protein, mouse
  • Lymphoid Enhancer-Binding Factor 1
  • Regulatory Sequences, Ribonucleic Acid
  • Interleukin-4