Cutting edge: Autoantigen Ro52 is an interferon inducible E3 ligase that ubiquitinates IRF-8 and enhances cytokine expression in macrophages
Cutting edge: Autoantigen Ro52 is an interferon inducible E3 ligase that ubiquitinates IRF-8 and enhances cytokine expression in macrophages
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DOI：
10.4049/jimmunol.179.1.26
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发表时间：
2007-07-01
影响因子：
4.4
通讯作者：
Ozato, Keiko
中科院分区：
文献类型：
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作者：
Kong, Hee Jeong;Anderson, D. Eric;Ozato, Keiko
干扰素调节因子（IRF）-8是一种对巨噬细胞的发育和功能非常重要的转录因子。它在细胞因子基因（包括IL-12 p40）的诱导中起关键作用。免疫纯化和质谱分析发现，在IFN-γ和TLR刺激后，IRF-8与小鼠巨噬细胞中的Ro 52相互作用。Ro 52是干扰素诱导的TRIM家族蛋白，是干燥综合征和系统性红斑狼疮患者的自身抗原。Ro 52有一个RING基序，能够泛素化自身。我们发现，IRF-8是泛素化的Ro 52在体内和体外。Ro 52的异位表达以IRF-8依赖的方式增强IFN-γ/TLR刺激的巨噬细胞中IL-12 p40的表达。Ro 52是IRF-8的E3连接酶，其在泛素化的非降解途径中起作用，并有助于引发巨噬细胞中的先天免疫。
IFN regulatory factor (IRF)-8 is a transcription factor important for the development and function of macrophages. It plays a critical role in the induction of cytokine genes, including IL-12p40. Immunopurification and mass spectrometry analysis found that IRF-8 interacted with Ro52 in murine macrophages upon IFN-gamma and TLR stimulation. Ro52 is an IFN-inducible protein of the tripartite motif (TRIM) family and is an autoantigen present in patients with Sjogren's syndrome and systemic lupus erythematosus. Ro52 has a RING motif and is capable of ubiquitinating itself. We show that IRF-8 is ubiquitinated by Ro52 both in vivo and in vitro. Ectopic expression of Ro52 enhanced IL-12p40 expression in IFN-gamma/TLR-stimulated macrophages in an IRF-8-dependent manner. Together, Ro52 is an E3 ligase for IRF-8 that acts in a non-degradation pathway of ubiquitination, and contributes to the elicitation of innate immunity in macrophages.