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Inhibition of Suppressive T Cell Factor 1 (TCF-1) Isoforms in Naive CD4+ T Cells Is Mediated by IL-4/STAT6 Signaling
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Maier, E., Hebenstreit, Daniel, Posselt, G., Hammerl, P., Duschl, A. and Horejs-Hoeck, J. (2011) Inhibition of Suppressive T Cell Factor 1 (TCF-1) Isoforms in Naive CD4+ T Cells Is Mediated by IL-4/STAT6 Signaling. Journal of Biological Chemistry, Vol. 286 (No. 2). pp. 919-928. doi:10.1074/jbc.M110.144949 ISSN 0021-9258.
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Official URL: http://dx.doi.org/10.1074/jbc.M110.144949
Abstract
The Wnt pathway transcription factor T cell factor 1 (TCF-1) plays essential roles in the control of several developmental processes, including T cell development in the thymus. Although previously regarded as being required only during early T cell development, recent studies demonstrate an important role for TCF-1 in T helper 2 (Th2) cell polarization. TCF-1 was shown to activate expression of the Th2 transcription factor GATA-binding protein 3 (GATA3) and thus to promote the development of IL-4-producing Th2 cells independent of STAT6 signaling. In this study, we show that TCF-1 is down-regulated in human naive CD4+ T cells cultured under Th2-polarizing conditions. The down-regulation is largely due to the polarizing cytokine IL-4 because IL-4 alone is sufficient to substantially inhibit TCF-1 expression. The IL-4-induced suppression of TCF-1 is mediated by STAT6, as shown by electrophoretic mobility shift assays, chromatin immunoprecipitation, and STAT6 knockdown experiments. Moreover, we found that IL-4/STAT6 predominantly inhibits the shorter, dominant-negative TCF-1 isoforms, which were reported to inhibit IL-4 transcription. Thus, this study provides a model for an IL-4/STAT6-dependent fine tuning mechanism of TCF-1-driven T helper cell polarization.
Item Type: | Journal Article | ||||
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||
Journal or Publication Title: | Journal of Biological Chemistry | ||||
Publisher: | American Society for Biochemistry and Molecular Biology | ||||
ISSN: | 0021-9258 | ||||
Official Date: | 2011 | ||||
Dates: |
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Volume: | Vol. 286 | ||||
Number: | No. 2 | ||||
Page Range: | pp. 919-928 | ||||
DOI: | 10.1074/jbc.M110.144949 | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published | ||||
Access rights to Published version: | Restricted or Subscription Access |
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