Activation of STAT6 by STING Is Critical for Antiviral Innate Immunity

被引:317
|
作者
Chen, Huihui [1 ,2 ]
Sun, Hui [1 ,2 ]
You, Fuping [1 ,2 ]
Sun, Wenxiang [1 ,2 ]
Zhou, Xiang [1 ,2 ]
Chen, Lu [1 ,2 ]
Yang, Jing [1 ,2 ]
Wang, Yutao [1 ,2 ]
Tang, Hong [1 ,2 ]
Guan, Yukun [1 ,2 ]
Xia, Weiwei [1 ]
Gu, Jun [1 ]
Ishikawa, Hiroki [4 ,5 ]
Gutman, Delia [4 ,5 ]
Barber, Glen [4 ,5 ]
Qin, Zhihai [6 ]
Jiang, Zhengfan [1 ,2 ,3 ]
机构
[1] Peking Univ, Sch Life Sci, State Key Lab Prot & Plant Gene Res, Beijing 100871, Peoples R China
[2] Peking Univ, Sch Life Sci, Key Lab Cell Proliferat & Differentiat, Minist Educ, Beijing 100871, Peoples R China
[3] Tsinghua Univ, Peking Univ, Joint Ctr Life Sci, Beijing 100084, Peoples R China
[4] Univ Miami, Sch Med, Dept Med, Miami, FL 33136 USA
[5] Univ Miami, Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA
[6] Inst Biophys, State Key Lab Biomacromol, Beijing, Peoples R China
关键词
NF-KAPPA-B; RIG-I; ADAPTER PROTEIN; CYTOSOLIC DNA; EXPRESSION; ALPHA; CELLS; INTERLEUKIN-4; RECOGNITION; RESPONSES;
D O I
10.1016/j.cell.2011.09.022
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:436 / 446
页数:11
相关论文
共 50 条
  • [41] Expression of STAT6 and Phosphorylated STAT6 in Primary Central Nervous System Lymphomas
    Karpathiou, Georgia
    Ferrand, Elise
    Camy, Florian
    Babiuc, Silvia-Maria
    Papoudou-Bai, Alexandra
    Dumollard, Jean Marc
    Cornillon, Jerome
    Peoc'h, Michel
    JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 2021, 80 (09): : 830 - 834
  • [42] Interleukin-4-induced transcriptional activation by Stat6 involves multiple serine/threonine kinase pathways and serine phosphorylation of Stat6
    Pesu, M
    Takaluoma, K
    Aittomäki, S
    Lagerstedt, A
    Saksela, K
    Kovanen, PE
    Silvennoinen, O
    BLOOD, 2000, 95 (02) : 494 - 502
  • [43] The biology of Stat4 and Stat6
    Wurster, AL
    Tanaka, T
    Grusby, MJ
    ONCOGENE, 2000, 19 (21) : 2577 - 2584
  • [44] Interleukin 4-dependent Stat6 activation in lymphocytes is critical for cholestasis-induced hepatic fibrosis
    Hines, Ian N.
    Kremer, Michael
    Perry, Ashley W.
    Milton, Richard J.
    Wheeler, Michael D.
    GASTROENTEROLOGY, 2007, 132 (04) : A750 - A751
  • [45] The biology of Stat4 and Stat6
    Andrea L Wurster
    Takashi Tanaka
    Michael J Grusby
    Oncogene, 2000, 19 : 2577 - 2584
  • [46] STAT6 promotes innate immunity against BEFV and VSV by inhibiting STUB1 and NIX-mediated MAVS degradation
    Zhang, Fuzhen
    Wang, Hongmei
    He, Hongbin
    Hou, Peili
    VETERINARY MICROBIOLOGY, 2024, 298
  • [47] Targeting STAT6 in PMBL
    Leroy, Karen
    Pujals, Anais
    Pelletier, Laura
    ONCOTARGET, 2014, 5 (17) : 7216 - 7216
  • [48] Regulation of IL-4-induced STAT6 activation by SUMOylation
    Lee, Choong-Eun
    Tran, Tam
    Kim, Seol-Hee
    Sung, Ki-Sa
    Choi, Cheol-Yong
    JOURNAL OF IMMUNOLOGY, 2013, 190
  • [49] The roles of STAT6 in regulating B cell fate, activation, and function
    Wang, Wei
    Wang, Luman
    Zha, Bingbing
    IMMUNOLOGY LETTERS, 2021, 233 : 87 - 91
  • [50] Malarial anemia and STAT6
    Robson, Kathryn J. H.
    Weatherall, David J.
    HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 2009, 94 (02): : 157 - 159