LEF-1 negatively controls interleukin-4 expression through a proximal promoter regulatory element.
J Biol Chem. 2008 Jun 25;
Authors: Hebenstreit D, Giaisi M, Treiber MK, Zhang XB, Mi HF, Horejs-Hoeck J, Andersen KG, Krammer PH, Duschl A, Li-Weber M
Lymphoid enhancer binding factor (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 expressions from the developing Th2 cells that over-express 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. Knock-down LEF-1 expression by LEF-1-specific siRNA 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.
PMID: 18579517 [PubMed - as supplied by publisher]
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PubMed: Wnt
NCBI: db=PubMed; Term=Wnt
