p120-catenin promotes innate antiviral immunity through stabilizing TBK1-IRF3 complex

Haifeng Wu; Xiuqing Yan; Liang Zhao; Xiang Li; Ximing Li; Yi Zhang; Changping Gu; Fan Yang; Jingting Yan; Yalin Lou; Yufei Li; Li Yang; Xiaofeng Qin; Yuelan Wang

doi:10.1016/j.molimm.2023.03.013

p120-catenin promotes innate antiviral immunity through stabilizing TBK1-IRF3 complex

Mol Immunol. 2023 May:157:8-17. doi: 10.1016/j.molimm.2023.03.013. Epub 2023 Mar 21.

Authors

Haifeng Wu¹, Xiuqing Yan¹, Liang Zhao¹, Xiang Li¹, Ximing Li², Yi Zhang¹, Changping Gu³, Fan Yang³, Jingting Yan³, Yalin Lou³, Yufei Li³, Li Yang³, Xiaofeng Qin³, Yuelan Wang⁴

Affiliations

¹ Shandong Provincial Qianfoshan Hospital, Shandong University, No. 16766 Jingshi Road, Jinan 250014, Shandong, China; Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Shandong First Medical University, Shandong Institute of Anesthesia and Respiratory Critical Care Medicine, No. 16766 Jingshi Road, Jinan 250014, Shandong, China.
² Linyi People's Hospital, Department of Anesthesiology, Lanshan District Wuhan Road and Wohushan Road Intersection, Linyi 276000, China.
³ Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Shandong First Medical University, Shandong Institute of Anesthesia and Respiratory Critical Care Medicine, No. 16766 Jingshi Road, Jinan 250014, Shandong, China.
⁴ Shandong Provincial Qianfoshan Hospital, Shandong University, No. 16766 Jingshi Road, Jinan 250014, Shandong, China; Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Shandong First Medical University, Shandong Institute of Anesthesia and Respiratory Critical Care Medicine, No. 16766 Jingshi Road, Jinan 250014, Shandong, China. Electronic address: wyldgf@163.com.

PMID: 36958140
DOI: 10.1016/j.molimm.2023.03.013

Abstract

TBK1-IRF3 complex plays vital roles in antiviral immune responses, its regulatory mechanisms are currently incompletely understood. p120-catenin (p120), an armadillo-repeat protein, mainly regulates the stability of classical cadherins and the development of epithelial-to-mesenchymal transitions (EMTs). Here we report that p120 is a positive regulator of type I IFN production. Ectopic expression of p120 enhanced Vesicular stomatitis virus and Sendai-virus-induced type I IFN production, whereas knockdown of p120 expression suppressed type I IFN production. Mechanistically, p120 promoted phosphorylation of IRF3 via stabilizing the TBK1-IRF3 complex. Consistently, p120 knock down mice are more susceptible to VSV infection as indicated by higher tissue viral titers, less IFN-I production and greater infiltration of immune cells. This study reveals p120 as an important positive regulator in innate immunity and identifies that p120 facilitates host antiviral response through stabilizing TBK1-IRF3 complex.

Keywords: Innate immunity; P120-catenin; TBK1-IRF3 complex; Type I interferon; Virus infection.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antiviral Agents
Delta Catenin
Immunity, Innate
Interferon Regulatory Factor-3 / metabolism
Interferon Type I*
Mice
Phosphorylation
Protein Serine-Threonine Kinases* / metabolism

Substances

Protein Serine-Threonine Kinases
Delta Catenin
Antiviral Agents
Interferon Type I
Interferon Regulatory Factor-3
Tbk1 protein, mouse
Irf3 protein, mouse