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Toxicol Sci：通过下调IL-7受体/ Pax5信号，钨阻断小鼠B淋巴细胞分化和增殖

2019-03-27 不详 网络

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钨是一种与几种儿科白血病群相关的新兴环境毒物，尽管尚未建立起因果关系。我们之前的研究表明，钨暴露导致骨髓中前B细胞的积累，这种细胞类型在小儿急性淋巴细胞白血病（ALL）中累积。为了更好地理解相关的分子机制，我们对来自对照和暴露于钨的小鼠的流式分选的前B细胞进行了RNA测序。结果显示，钨降低了对B细胞发育至关重要的多个基因的表达，包括IL-7R和前BCR信号传导途径的成员，例如Jak1，Stat5a

钨是一种与几种儿科白血病群相关的新兴环境毒物，尽管尚未建立起因果关系。我们之前的研究表明，钨暴露导致骨髓中前B细胞的积累，这种细胞类型在小儿急性淋巴细胞白血病（ALL）中累积。

为了更好地理解相关的分子机制，我们对来自对照和暴露于钨的小鼠的流式分选的前B细胞进行了RNA测序。结果显示，钨降低了对B细胞发育至关重要的多个基因的表达，包括IL-7R和前BCR信号传导途径的成员，例如Jak1，Stat5a，Pax5，Syk和Ikzf3。这些结果在B细胞分化的体外模型中得到证实，其中钨在pro-B细胞阶段停止分化并抑制增殖。这些变化与IL-7R信号传导通路中多个基因的表达降低和IL-7R，磷酸化STAT5（pSTAT5）双阳性细胞的百分比降低相关。补充IL-7或过表达Pax5（IL-7R下游的转录因子）拯救了钨诱导的分化阻滞。

总之，这些数据支持IL-7R/Pax5信号轴对于钨介导的对B细胞前期发育的影响至关重要的假设。

原始出处：

Wu T, Bolt AM, et al., Tungsten Blocks Murine B Lymphocyte Differentiation and Proliferation Through Downregulation of IL-7 Receptor/Pax5 Signaling. Toxicol Sci. 2019 Mar 26. pii: kfz080. doi: 10.1093/toxsci/kfz080.

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    2019-08-31 41514497@qq.com

    #阻断#

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    2019-10-17 fengting15

    #B淋巴细胞#

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    2019-03-29 wetgdt

    #淋巴细胞#

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    2019-03-29 karmond

    #细胞分化#

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