PMID- 20980261
OWN - NLM
STAT- MEDLINE
DCOM- 20110302
LR  - 20211020
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 286
IP  - 2
DP  - 2011 Jan 14
TI  - Inhibition of suppressive T cell factor 1 (TCF-1) isoforms in naive CD4+ T cells 
      is mediated by IL-4/STAT6 signaling.
PG  - 919-28
LID - 10.1074/jbc.M110.144949 [doi]
AB  - 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.
FAU - Maier, Elisabeth
AU  - Maier E
AD  - Department of Molecular Biology, University of Salzburg, Hellbrunner Strasse 34, 
      A-5020 Salzburg, Austria.
FAU - Hebenstreit, Daniel
AU  - Hebenstreit D
FAU - Posselt, Gernot
AU  - Posselt G
FAU - Hammerl, Peter
AU  - Hammerl P
FAU - Duschl, Albert
AU  - Duschl A
FAU - Horejs-Hoeck, Jutta
AU  - Horejs-Hoeck J
LA  - eng
GR  - MC_U105161047/MRC_/Medical Research Council/United Kingdom
GR  - P 18409/FWF_/Austrian Science Fund FWF/Austria
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101027
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Hepatocyte Nuclear Factor 1-alpha)
RN  - 0 (Hnf1a protein, mouse)
RN  - 0 (IL4 protein, human)
RN  - 0 (LEF1 protein, human)
RN  - 0 (Lef1 protein, mouse)
RN  - 0 (Lymphoid Enhancer-Binding Factor 1)
RN  - 0 (STAT6 Transcription Factor)
RN  - 0 (STAT6 protein, human)
RN  - 0 (Stat6 protein, mouse)
RN  - 0 (T Cell Transcription Factor 1)
RN  - 0 (TCF7 protein, human)
RN  - 207137-56-2 (Interleukin-4)
SB  - IM
MH  - Animals
MH  - CD4-Positive T-Lymphocytes/cytology/immunology/*metabolism
MH  - Cell Polarity/*immunology
MH  - Cells, Cultured
MH  - Gene Expression/immunology
MH  - Hepatocyte Nuclear Factor 1-alpha
MH  - Humans
MH  - Immunologic Memory/immunology
MH  - Interleukin-4/immunology/*metabolism
MH  - Lymphoid Enhancer-Binding Factor 1/genetics/immunology/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Mutant Strains
MH  - STAT6 Transcription Factor/genetics/immunology/*metabolism
MH  - Signal Transduction/*immunology
MH  - T Cell Transcription Factor 1/genetics/immunology/*metabolism
PMC - PMC3019123
MID - UKMS33363
OID - NLM: UKMS33363
EDAT- 2010/10/29 06:00
MHDA- 2011/03/03 06:00
PMCR- 2012/01/14
CRDT- 2010/10/29 06:00
PHST- 2010/10/29 06:00 [entrez]
PHST- 2010/10/29 06:00 [pubmed]
PHST- 2011/03/03 06:00 [medline]
PHST- 2012/01/14 00:00 [pmc-release]
AID - S0021-9258(20)56280-7 [pii]
AID - M110.144949 [pii]
AID - 10.1074/jbc.M110.144949 [doi]
PST - ppublish
SO  - J Biol Chem. 2011 Jan 14;286(2):919-28. doi: 10.1074/jbc.M110.144949. Epub 2010 
      Oct 27.