Ouyang W, Ranganath S H, Weindel K, Bhattacharya D, Murphy T L, Sha W C, Murphy K M
Department of Pathology and Center for Immunology, Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Immunity. 1998 Nov;9(5):745-55. doi: 10.1016/s1074-7613(00)80671-8.
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.
最近，转录因子GATA-3被证明在Th2细胞而非Th1细胞中选择性表达，并增强Th2特异性细胞因子。在此，我们表明，发育中的Th1细胞中GATA-3表达的缺失需要通过Stat4的IL-12信号传导，而不仅仅是由于缺乏IL-4所致。此外，我们证明了GATA-3在直接抑制Th1发育方面具有新的作用，这与其对Th2特异性细胞因子的正向作用不同。GATA-3通过一种不依赖于IL-4的细胞内在机制抑制Th1细胞因子，这种机制可能涉及对IL-12信号传导的抑制。因此，GATA-3表达和IL-12信号传导相互拮抗，这有助于在早期Th发育过程中一种途径的快速主导，从而在细胞因子谱中产生稳定的差异。
