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Cell子刊：中科院生化所发现TET3调节I型干扰素合成的新机制

2016-07-21 佚名 生物谷

TET3干扰素
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近日，中国科学院上海生化所王红艳研究员在国际学术期刊Cell Reports上发表了一篇题为“TET3 inhibits type I IFN production independent of DNA demethylation”的最新研究进展，该工作揭示DNA去甲基化酶TET3以一种新型的作用机制，负向调控I型干扰素合成，进而影响宿主清除病毒的能力。 I型干扰素在抗病毒应答中扮演双重角

近日，中国科学院上海生化所王红艳研究员在国际学术期刊Cell Reports上发表了一篇题为“TET3 inhibits type I IFN production independent of DNA demethylation”的最新研究进展，该工作揭示DNA去甲基化酶TET3以一种新型的作用机制，负向调控I型干扰素合成，进而影响宿主清除病毒的能力。

I型干扰素在抗病毒应答中扮演双重角色：既发挥有益作用，又存在有害作用。在急性病毒感染过程中，I型干扰素通过直接或间接诱导干扰素激活的相关基因，抑制病毒的复制和传播。此外，I型干扰素也能参与自身免疫性疾病调控，但系统性红斑狼疮的发生发展也与I型干扰素密切相关。因此需要了解宿主体内I型IFN的精确调节过程才能有助于预防免疫功能紊乱。

在这项最新研究中，研究人员发现DNA去甲基化酶TET3是poly（I:C）刺激或病毒感染应答过程中IFN-beta的一个负向调控因子。删除TET3能够增强抗病毒应答，同时IFN-beta表达增加，IFN激活的相关基因表达也增加。

通过对TET3进行分析研究人员发现TET3的催化结构域对抑制IFN-beta合成有着非常重要的作用，但该过程却并不依赖于TET3的酶活性。他们发现TET3通过催化结构域与去乙酰化酶HDAC1和转录调控因子SIN3A发生相互作用，增强了这两个分子与Ifnb1启动子的结合。

这项研究表明TET3能够负向调控I型IFN的合成，并且该过程并不依赖于DNA去甲基化。这不仅说明TET3在免疫细胞中可发挥信号蛋白作用进行基因调控，还将有助于开发预防I型IFN相关疾病的新策略。

原始出处

Shengjie Xue1, 4, Chang Liu1, 4, Xiujie Sun1, Weiyun Li1, Chi Zhang1, Xin Zhou1, Yao Lu1, Jun Xiao1,Chunyang Li1, Xiaoyan Xu1, Bing Sun2, Guoliang Xu3, Hongyan Wang1.TET3 Inhibits Type I IFN Production Independent of DNA Demethylation.Cell Reports.2016

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    2017-04-28 维他命

    #CEL#

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    2017-03-11 yhy100200

    #TET#

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    2016-12-07 zhaozhouchifen

    #Cell#

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    2017-06-29 gous

    #中科院#

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    2016-07-23 风铃821

    #I型干扰素#

    0