Division of Protein and Nucleic Acid Chemistry, Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.
Nat Immunol. 2013 Apr;14(4):327-36. doi: 10.1038/ni.2548. Epub 2013 Mar 3.
During pathogen infection, antibodies can be carried into the infected cell, where they are detected by the ubiquitously expressed cytosolic antibody receptor TRIM21. Here we found that recognition of intracellular antibodies by TRIM21 activated immune signaling. TRIM21 catalyzed the formation of Lys63 (K63)-linked ubiquitin chains and stimulated the transcription factor pathways of NF-κB, AP-1, IRF3, IRF5 and IRF7. Activation resulted in the production of proinflammatory cytokines, modulation of natural killer stress ligands and induction of an antiviral state. Intracellular antibody signaling was abrogated by genetic deletion of TRIM21 and was restored by ectopic expression of TRIM21. The sensing of antibodies by TRIM21 was stimulated after infection by DNA or RNA nonenveloped viruses or intracellular bacteria. Thus, the antibody-TRIM21 detection system provides potent, comprehensive activation of the innate immune system independently of known pattern-recognition receptors.
在病原体感染期间，抗体可以被带入感染细胞，在那里它们被广泛表达的细胞质抗体受体 TRIM21 检测到。在这里，我们发现 TRIM21 对细胞内抗体的识别激活了免疫信号。TRIM21 催化 Lys63（K63）连接的泛素链的形成，并刺激 NF-κB、AP-1、IRF3、IRF5 和 IRF7 转录因子途径。激活导致促炎细胞因子的产生、自然杀伤应激配体的调节和抗病毒状态的诱导。TRIM21 的基因缺失会阻断细胞内抗体信号，而 TRIM21 的异位表达则会恢复该信号。TRIM21 对 DNA 或 RNA 无包膜病毒或细胞内细菌感染后的抗体检测受到刺激。因此，抗体-TRIM21 检测系统独立于已知的模式识别受体，为固有免疫系统提供了强大而全面的激活。
