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首页> 外文期刊>Immunology: An Official Journal of the British Society for Immunology >A continuous T-bet expression is required to silence the interleukin-4-producing potential in T helper type 1 cells.
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A continuous T-bet expression is required to silence the interleukin-4-producing potential in T helper type 1 cells.

机译:需要连续的T-bet表达以沉默1型T辅助细胞中产生白介素4的潜能。

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摘要

To develop into committed T helper type 1 (Th1) cells, naive CD4(+) T cells not only need to acquire the capacity to produce interferon-gamma (IFN-gamma), but they also need to gain the ability to silence their interleukin-4 (IL-4) -producing potential. How Th1 cells silence their Th2 cytokine-producing potential is an important yet unresolved issue in Th1 immunity. We found that a lack of IL-4 stimulation was not sufficient to silence the IL-4-producing potential in activated CD4(+) T cells and that Th1-promoting factor was required. Although it has been shown that T-bet is a crucial factor in suppressing Il4 gene expression, it is unclear whether a continuous presence of T-bet is required to silence the Il4 gene in Th1 cells. To address this problem, we used an inducible form of T-bet - a T-bet-oestrogen receptor fusion molecule (T-bet-ER). We found that the activation of T-bet during primary or secondary culture was sufficient to silence IL-4-producing potential. On the other hand, the inactivation of T-bet after naive CD4(+) T cells had differentiated into Th1 cells resulted in derepression of Il4 gene transcription. Additionally, we found that T-bet is required to maintain Ifng expression. Our data demonstrate that the continuous expression of T-bet is required for Th1 cells to silence their IL-4-producing potential.
机译:要发展成为定型的T辅助1型(Th1)细胞,幼稚的CD4(+)T细胞不仅需要获得产生干扰素-γ(IFN-γ)的能力,而且还需要获得沉默白细胞介素的能力。 -4(IL-4)产生潜力。 Th1细胞如何沉默其产生Th2细胞因子的潜力是Th1免疫力中一个重要但尚未解决的问题。我们发现缺乏IL-4刺激不足以使激活的CD4(+)T细胞中产生IL-4的潜力沉默,并且需要Th1促进因子。尽管已经显示T-bet是抑制Il4基因表达的关键因素,但尚不清楚是否需要连续存在T-bet才能沉默Th1细胞中的Il4基因。为了解决这个问题,我们使用了T-bet的可诱导形式-T-bet-雌激素受体融合分子(T-bet-ER)。我们发现在原代或继代培养过程中T-bet的激活足以使产生IL-4的潜力沉默。另一方面,幼稚的CD4(+)T细胞分化为Th1细胞后T-bet的失活导致Il4基因转录的抑制。此外,我们发现维持Ingng表达需要T-bet。我们的数据表明,Th1细胞需要连续表达T-bet,才能沉默其产生IL-4的潜力。

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