TY - JOUR
T1 - Inhibition of Th1 development mediated by GATA-3 through an IL-4- independent mechanism
AU - Ouyang, Wenjun
AU - Ranganath, Sheila H.
AU - Weindel, Kathryn
AU - Bhattacharya, Deepta
AU - Murphy, Theresa L.
AU - Sha, William C.
AU - Murphy, Kenneth M.
N1 - Funding Information:
We thank J. D. Engel (Evanston, IL) for the R/M GATA-3 plasmid, A. Winoto (Berkeley, CA) for providing the human version of the KRR GATA-3 mutant, and Debbie Wyman for excellent cell sorting. This work was supported by National Institutes of Health grants AI31238 and AIDK39676. K. M. M. is an Associate Investigator of the Howard Hughes Medical Institute.
PY - 1998/11
Y1 - 1998/11
N2 - 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.
AB - 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.
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U2 - 10.1016/S1074-7613(00)80671-8
DO - 10.1016/S1074-7613(00)80671-8
M3 - Article
C2 - 9846495
AN - SCOPUS:0032212793
SN - 1074-7613
VL - 9
SP - 745
EP - 755
JO - Immunity
JF - Immunity
IS - 5
ER -