LSm14A Plays a Critical Role in Antiviral Immune Responses by Regulating MITA Level in a Cell-Specific Manner
LSm14A Plays a Critical Role in Antiviral Immune Responses by Regulating MITA Level in a Cell-Specific Manner
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LSm14A 通过以细胞特异性方式调节 MITA 水平，在抗病毒免疫反应中发挥关键作用
DOI：
10.4049/jimmunol.1600212
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发表时间：
2016-06-15
影响因子：
4.4
通讯作者：
Shu, Hong-Bing
中科院分区：
文献类型：
--
作者：
Liu, Tian-Tian;Yang, Qing;Shu, Hong-Bing
病毒感染引发抗病毒细胞因子和效应物的诱导，它们是先天性抗病毒免疫应答的关键介质。已经表明，加工体相关蛋白LSm 14 A参与细胞系中抗病毒细胞因子的诱导，但缺乏体内证据。通过产生LSm 14 A缺陷小鼠，在这项研究中，我们表明LSm 14 A在树突状细胞（DC）中诱导抗病毒细胞因子中起着关键和特异性的作用，但在巨噬细胞和成纤维细胞中则不然。由DNA病毒HSV-1和鼠疱疹病毒68和RNA病毒水泡性口炎病毒而不是仙台病毒引发的抗病毒细胞因子的诱导在Lsm 14 a 2/2 DC中受损，这与接头蛋白MITA/STING在抗病毒信号通路中的功能相关。LSm 14 A缺陷通过损害其核mRNA前体加工特异性下调DC中的MITA/STING水平，随后损害抗病毒先天性和适应性免疫应答。我们的研究结果揭示了抗病毒免疫反应的核mRNA前体加工和细胞特异性调节机制。
Viral infection triggers induction of antiviral cytokines and effectors, which are critical mediators of innate antiviral immune response. It has been shown that the processing body-associated protein LSm14A is involved in the induction of antiviral cytokines in cell lines but in vivo evidence is lacking. By generating LSm14A-deficient mice, in this study, we show that LSm14A plays a critical and specific role in the induction of antiviral cytokines in dendritic cells (DCs) but not in macrophages and fibroblasts. Induction of antiviral cytokines triggered by the DNAviruses HSV-1 and murid herpesvirus 68 and the RNAvirus vesicular stomatitis virus but not Sendai virus was impaired in Lsm14a 2/2 DCs, which is correlated to the functions of the adaptor protein MITA/STING in the antiviral signaling pathways. LSm14A deficiency specifically downregulated MITA/STING level in DCs by impairing its nuclear mRNA precursor processing and subsequently impaired antiviral innate and adaptive immune responses. Our findings reveal a nuclear mRNA precursor processing and cell-specific regulatory mechanism of antiviral immune responses.