Inhibition of Th1 development mediated by GATA-3 through an IL-4-independent mechanism.
Recently, the transcription factor GATA-3 was shown to be selectively expressed in Th2 but not Th1 cells and to augment Th2-specific cytokines. Here, we show that loss of GATA-3 expression by developing Th1 cells requires IL-12 signaling through Stat4 and does not simply result from an absence of IL-4. Moreover, we demonstrate a novel role for GATA-3 in directly repressing Th1 development distinct from its positive actions on Th2-specific cytokines. GATA-3 inhibits Th1 cytokines by a cell-intrinsic mechanism that is not dependent on IL-4 and that may involve repression of IL-12 signaling. Thus, GATA-3 expression and IL-12 signaling are mutually antagonistic, which facilitates rapid dominance of one pathway during early Th development, producing a stable divergence in cytokine profiles.
Ouyang
W
W
Department of Pathology and Center for Immunology, Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Ranganath
S H
SH
Weindel
K
K
Bhattacharya
D
D
Murphy
T L
TL
Sha
W C
WC
Murphy
K M
KM
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D004268:DNA-Binding Proteins / Q000502:physiology*; D050990:GATA3 Transcription Factor; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D018123:Receptors, Interleukin / Q000096:biosynthesis; D053707:Receptors, Interleukin-12; D050797:STAT4 Transcription Factor; D015398:Signal Transduction / Q000502:physiology; D018417:Th1 Cells / Q000166:cytology* / Q000502:physiology; D015534:Trans-Activators / Q000502:physiology*
D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; C494748:Gata3 protein, mouse; D007376:Interleukin-2; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; C494091:Stat4 protein, mouse; D015534:Trans-Activators; D015847:Interleukin-4; D007371:Interferon-gamma