Activation of STAT6 by STING Is Critical for Antiviral Innate Immunity
Activation of STAT6 by STING Is Critical for Antiviral Innate Immunity
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DOI：
10.1016/j.cell.2011.09.022
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发表时间：
2011-10-14
期刊：
影响因子：
64.5
通讯作者：
Jiang, Zhengfan
中科院分区：
文献类型：
--
作者：
Chen, Huihui;Sun, Hui;Jiang, Zhengfan
STAT 6通过转导来自细胞外细胞因子的信号在获得性免疫中起着重要作用。我们现在表明，STAT 6是响应病毒感染的先天免疫信号所必需的。病毒或细胞质核酸触发STING（也称为MITA/ERIS）将STAT 6募集到内质网，导致STAT 6在Ser（407）上被TBK 1和Tyr（641）磷酸化，而不依赖于JAK。磷酸化的STAT 6然后二聚化并易位到细胞核以诱导负责免疫细胞归巢的特异性靶基因。在所有测试的细胞类型中检测到病毒诱导的STAT 6活化，这与STAT 6在细胞因子信号传导中的细胞类型特异性作用相反，并且Stat 6（-/-）小鼠对病毒感染易感。因此，STAT 6介导免疫信号传导以响应质膜上的细胞因子和内质网上的病毒感染。
STAT6 plays a prominent role in adaptive immunity by transducing signals from extracellular cytokines. We now show that STAT6 is required for innate immune signaling in response to virus infection. Viruses or cytoplasmic nucleic acids trigger STING (also named MITA/ERIS) to recruit STAT6 to the endoplasmic reticulum, leading to STAT6 phosphorylation on Ser(407) by TBK1 and Tyr(641), independent of JAKs. Phosphorylated STAT6 then dimerizes and translocates to the nucleus to induce specific target genes responsible for immune cell homing. Virus-induced STAT6 activation is detected in all cell-types tested, in contrast to the cell-type specific role of STAT6 in cytokine signaling, and Stat6(-/-) mice are susceptible to virus infection. Thus, STAT6 mediates immune signaling in response to both cytokines at the plasma membrane, and virus infection at the endoplasmic reticulum.