T cell factor 1 initiates the T helper type 2 fate by inducing the transcription factor GATA-3 and repressing interferon-gamma.
The differentiation of activated CD4(+) T cells into the T helper type 1 (T(H)1) or T(H)2 fate is regulated by cytokines and the transcription factors T-bet and GATA-3. Whereas interleukin 12 (IL-12) produced by antigen-presenting cells initiates the T(H)1 fate, signals that initiate the T(H)2 fate are not completely characterized. Here we show that early GATA-3 expression, required for T(H)2 differentiation, was induced by T cell factor 1 (TCF-1) and its cofactor beta-catenin, mainly from the proximal Gata3 promoter upstream of exon 1b. This activity was induced after T cell antigen receptor (TCR) stimulation and was independent of IL-4 receptor signaling through the transcription factor STAT6. Furthermore, TCF-1 blocked T(H)1 fate by negatively regulating interferon-gamma (IFN-gamma) expression independently of beta-catenin. Thus, TCF-1 initiates T(H)2 differentiation of activated CD4(+) T cells by promoting GATA-3 expression and suppressing IFN-gamma expression.
Yu
Qing
Q
Lymphocyte Development Unit, Laboratory of Immunology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.
Sharma
Archna
A
Oh
Sun Young
SY
Moon
Hyung-Geun
HG
Hossain
M Zulfiquer
MZ
Salay
Theresa M
TM
Leeds
Karen E
KE
Du
Hansen
H
Wu
Beibei
B
Waterman
Marian L
ML
Zhu
Zhou
Z
Sen
Jyoti Misra
JM
D000818:Animals; D002454:Cell Differentiation; D050990:GATA3 Transcription Factor / Q000235:genetics*; D007371:Interferon-gamma / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D051880:Receptors, Notch / Q000502:physiology; D051822:T Cell Transcription Factor 1 / Q000502:physiology*; D018418:Th2 Cells / Q000502:physiology*; D051176:beta Catenin / Q000502:physiology
D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D011948:Receptors, Antigen, T-Cell; D051880:Receptors, Notch; D051822:T Cell Transcription Factor 1; D051176:beta Catenin; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma