Ectopic expression of activated Stat6 induces the expression of Th2-specific cytokines and transcription factors in developing Th1 cells.
Stat6 is critical for IL-4-mediated Th2 cell development, but its molecular mechanism remains unclear. Here we constructed Stat6:ER, a Stat6-estrogen receptor fusion protein that can be activated by 4-hydroxy-tamoxifen, independently of IL-4 and endogenous Stat6. Retrovirus-mediated introduction of Stat6:ER into developing Th1 cells induced Th2-specific cytokines and suppressed IFNgamma production in a 4-HT-dependent manner and in the absence of IL-4. It also induced GATA-3 and c-maf expression and downregulated IL-12Rbeta2 chain expression. Its decreased ability to induce the Th2 phenotype with progressing Th1 cell commitment correlated with a decreased induction of GATA-3 and c-maf. This study indicates that Stat6 functions upstream of GATA-3 and c-Maf to induce Th2 development.
Kurata
H
H
Department of Immunobiology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, California 94304, USA.
Lee
H J
HJ
O'Garra
A
A
Arai
N
N
D000818:Animals; D001665:Binding Sites; D002455:Cell Division; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics*; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D050990:GATA3 Transcription Factor; D005786:Gene Expression Regulation; D005822:Genetic Vectors / Q000235:genetics; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics; D015847:Interleukin-4 / Q000276:immunology / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051257:Proto-Oncogene Proteins c-maf; D011960:Receptors, Estrogen / Q000819:agonists / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics; D012190:Retroviridae / Q000235:genetics; D050800:STAT6 Transcription Factor; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology; D018417:Th1 Cells / Q000187:drug effects / Q000378:metabolism*; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology*; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D015533:Transcriptional Activation
D016207:Cytokines; D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; C495608:Maf protein, mouse; D011518:Proto-Oncogene Proteins; D051257:Proto-Oncogene Proteins c-maf; D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D013629:Tamoxifen; C016601:afimoxifene; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma; D004247:DNA