Siglecl suppresses antiviral innate immune response by inducing TBK1 degradation via the ubiquitin ligase TRIM27  

作　　者：Qingliang Zheng Jin Hou Ye Zhou Yingyun Yang Bing Xie Xuetao Cao 

机构地区：[1]Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China [2]National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai 200433, China [3]National Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, China

出　　处：《Cell Research》2015年第10期1121-1136,共16页细胞研究（英文版）

摘　　要：Type I interferon （IFN） production plays pivotal roles in host antiviral innate immune responses, but an excessive production of type I IFN leads to the development of immunopathological conditions. Investigations on the regula- tory mechanisms underlying host type I IFN production are currently of great interest. Here, we found that the ex- pression of lectin family member Siglecl was upregulated by viral infection in macrophages, which was dependent on the IFN/JAK/STAT1 signaling pathway. Siglecl was found to negatively regulate viral infection-triggered type I IFN production. Mechanistically, Siglecl associates with DAP12 to recruit and activate the scaffolding function of SHP2; SHP2 then recruits E3 ubiquitin ligase TRIM27, which induces TBK1 degradation via K48-1inked ubiquitination at Lys251 and Lys372. Therefore, viral infection-induced upregulation of Siglecl feedback loop inhibits type I IFN pro- duction and suppresses antiviral innate immune responses. Our study outlines a novel mechanism of negative regula- tion of type I IFN production, which may help virus to escape immune elimination.

关 键 词：Siglec 1 innate immune response type I interferon TBK1 TRIM27 

分 类 号：Q939.4[生物学—微生物学] S852.4[农业科学—基础兽医学]