科学研究
LSm14A Plays a Critical Role in Antiviral Immune Responses by Regulating MITA Level in a Cell-Specific Manner.
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J Immunol.  2016 Jun 15;196(12):5101-11. doi: 10.4049/jimmunol.1600212. Epub 2016 May 4.

LSm14A Plays a Critical Role in Antiviral Immune Responses by Regulating MITA Level in a Cell-Specific Manner.

Liu TT 1,  Yang Q 1,  Li M 1,  Zhong B 1,  Ran Y 2,  Liu LL 2,  Yang Y 2,  Wang YY 2,  Shu HB 3.

Author information

  • 1College of Life Sciences, Medical Research Institute, Collaborative Innovation Center for Viral Immunology, State Key Laboratory of Virology, Wuhan University, Wuhan 430072, China; and.
  • 2Wuhan Institute of Virology, State Key Laboratory of Virology, Chinese Academy of Sciences, Wuhan 430071, China.
  • 3College of Life Sciences, Medical Research Institute, Collaborative Innovation Center for Viral Immunology, State Key Laboratory of Virology, Wuhan University, Wuhan 430072, China; and shuh@whu.edu.cn.

Abstract

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 DNA viruses HSV-1 and murid herpesvirus 68 and the RNA virus vesicular stomatitis virus but not Sendai virus was impaired in Lsm14a(-/-) 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.

PMID:  
27183626  
DOI:  
10.4049/jimmunol.1600212

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