Correlation between mRNA expression of Th1/Th2 cytokines and their specific transcription factors in human helper T-cell clones
Correlation between mRNA expression of Th1/Th2 cytokines and their specific transcription factors in human helper T-cell clones
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DOI：
10.1111/j.1440-1711.2005.01364.x
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发表时间：
2005-10-01
影响因子：
4
通讯作者：
Miyatake, S
中科院分区：
文献类型：
--
作者：
Kitamura, N;Kaminuma, O;Miyatake, S
人类 T 细胞 Th1/Th2 分化的机制尚未完全确定。在本研究中，一组人类 T 细胞克隆被用来阐明 Th1/Th2 特异性转录因子与人类辅助 T 细胞中细胞因子产生之间的关系。 Th1 克隆中 T-bet（一种 Th1 特异性转录因子）的 mRNA 表达水平高于 Th2 克隆。相反，Th2 克隆中 Th2 特异性转录因子（GATA-3 和 c-Maf）的诱导表达高于 Th1 克隆。各种T细胞克隆中T-bet的表达水平与IFN-γ的表达水平呈正相关，与Th2细胞因子尤其是IL-4的表达水平呈负相关。有趣的是，IL-3 和 IL-13 的表达（而非其他 Th2 细胞因子 IL-4 和 IL-5）的表达与 GATA-3 mRNA 水平密切相关。使用RNA干扰技术减少GATA-3可抑制IL-3和IL-13的表达，而GATA-3的过度表达可增强IL-3和IL-13的表达。总之，T-bet表达水平与Th1/Th2极化状态相关，而GATA-3是决定人T细胞产生IL-3和IL-13能力的关键因素。
The mechanisms that underlie Th1/Th2 differentiation of human T cells are incompletely defined. In the present study, a panel of human T-cell clones was used to elucidate the relationship between Th1/Th2-specific transcription factors and cytokine production in human helper T cells. The mRNA expression level of T-bet, a Th1-specific transcription factor, was higher in Th1 clones than in Th2 clones. In contrast, inducible expression of Th2-specific transcription factors (GATA-3 and c-Maf) in Th2 clones was higher than that in Th1 clones. The expression level of T-bet in various T-cell clones was positively correlated with that of IFN-gamma and negatively correlated with that of Th2 cytokines, particularly IL-4. Interestingly, the expression of IL-3 and IL-13, but not of other Th2 cytokines IL-4 and IL-5, was strongly correlated with GATA-3 mRNA levels. A reduction of GATA-3 using RNA interference technology suppressed, whereas overexpression of GATA-3 enhanced, the expression of IL-3 and IL-13. In conclusion, the level of T-bet expression is correlated with Th1/Th2 polarization status, whereas GATA-3 is a crucial factor in determining the IL-3 and IL-13 producing capacity of human T cells.