白细胞介素4:T细胞分化的信号传导机制和控制。

W E Paul
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引用次数: 83

摘要

白细胞介素4 (IL-4)是一种多效I型细胞因子,控制造血细胞和非造血细胞的生长和分化。它的受体是异二聚体。其中一条链,IL-4R α链,以高亲和力结合IL-4,并决定诱导的生化信号的性质。第二个链,伽马c,是产生这些信号所必需的。il -4介导的生长依赖于涉及IL-4R α Y497磷酸化的激活事件,导致造血细胞中4PS/IRS-2和非造血细胞中IRS-1的结合和磷酸化。相比之下,il -4介导的分化事件依赖于IL-4R α链更远的区域,包括一系列STAT-6结合位点。受体重建实验证实了这些受体结构域的独特作用。IL-4R α链的“生长”和“分化”结构域,作为与IL-2R β链的截断版本的嵌合结构独立表达,被证明将其功能传递给杂交受体。STAT-6在IL-4介导的基因激活和分化中的关键作用通过发现来自STAT-6敲除小鼠的淋巴细胞明显缺乏这些功能,但至少部分保留了生长能力,以响应IL-4而得以明确。IL-4在确定初始CD4+ T细胞表型中起核心作用。在IL-4存在的情况下,新启动的幼稚T细胞发育为IL-4产生细胞,而在IL-4不存在的情况下,它们优先成为γ -干扰素(ifn - γ)产生细胞。最近,一种特殊的T细胞亚群,CD4+/NK1.1+细胞,已被证明在刺激下产生大量的IL-4。这些细胞缺乏的两个例子被描述为- 2微球蛋白敲除小鼠和SJL小鼠。两者都表现出il -4生成细胞的发育缺陷,以及在多克隆刺激物抗igd刺激下血清IgE升高的缺陷。两组小鼠的CD4+/ NK1.1+ T细胞数量均显著减少,这强烈表明这些细胞在一些(但不是全部)生理刺激的IgE反应中发挥重要作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Interleukin 4: signalling mechanisms and control of T cell differentiation.

Interleukin 4 (IL-4) is a pleiotropic type I cytokine that controls both growth and differentiation among haemopoietic and non-haemopoietic cells. Its receptor is a heterodimer. One chain, the IL-4R alpha chain, binds IL-4 with high affinity and determines the nature of the biochemical signals that are induced. The second chain, gamma c, is required for the induction of such signals. IL-4-mediated growth depends upon activation events that involve phosphorylation of Y497 of IL-4R alpha, leading to the binding and phosphorylation of 4PS/IRS-2 in haemopoietic cells and of IRS-1 in non-haemopoietic cells. By contrast, IL-4-mediated differentiation events depend upon more distal regions of the IL-4R alpha chain that include a series of STAT-6 binding sites. The distinctive roles of these receptor domains was verified by receptor-reconstruction experiments. The 'growth' and 'differentiation' domains of the IL-4R alpha chain, independently expressed as chimeric structures with a truncated version of the IL-2R beta chain, were shown to convey their functions to the hybrid receptor. The critical role of STAT-6 in IL-4-mediated gene activation and differentiation was made clear by the finding that lymphocytes from STAT-6 knockout mice are strikingly deficient in these functions but have retained the capacity to grow, at least partially, in response to IL-4. IL-4 plays a central role in determining the phenotype of naive CD4+ T cells. In the presence of IL-4, newly primed naive T cells develop into IL-4 producers while in its absence they preferentially become gamma-interferon (IFN-gamma) producers. Recently, a specialized subpopulation of T cells, CD4+/NK1.1+ cells, has been shown to produce large amounts of IL-4 upon stimulation. Two examples of mice with deficiencies in these cells are described--beta 2-microglobulin knockout mice and SJL mice. Both show defects in the development of IL-4-producing cells and in the increase in serum IgE in response to stimulation with the polyclonal stimulant anti-IgD. Both sets of mice have major diminutions in the number of CD4+/ NK1.1+ T cells, strongly indicating an important role of these cells in some but not all IgE responses to physiologic stimuli.

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