Activation of STAT6 by STING is critical for antiviral innate immunity

Huihui Chen, Hui Sun, Fuping You, Wenxiang Sun, Xiang Zhou, Lu Chen, Jing Yang, Yutao Wang, Hong Tang, Yukun Guan, Weiwei Xia, Jun Gu, Hiroki Ishikawa, Delia Gutman, Glen Barber, Zhihai Qin, Zhengfan Jiang

Research output: Contribution to journalArticle

168 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)436-446
Number of pages11
JournalCell
Volume147
Issue number2
DOIs
StatePublished - Oct 14 2011

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Chen, H., Sun, H., You, F., Sun, W., Zhou, X., Chen, L., Yang, J., Wang, Y., Tang, H., Guan, Y., Xia, W., Gu, J., Ishikawa, H., Gutman, D., Barber, G., Qin, Z., & Jiang, Z. (2011). Activation of STAT6 by STING is critical for antiviral innate immunity. Cell, 147(2), 436-446. https://doi.org/10.1016/j.cell.2011.09.022