Ring Finger Protein 215 Negatively Regulates Type I IFN Production via Blocking NF-κB p65 Activation
Ring Finger Protein 215 Negatively Regulates Type I IFN Production via Blocking NF-κB p65 Activation
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无名指蛋白 215 通过阻断 NF-κB p65 激活负调节 I 型 IFN 产生
DOI：
10.4049/jimmunol.2200346
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发表时间：
2022-10
期刊：
影响因子：
--
通讯作者：
Zhenjian He
中科院分区：
文献类型：
--
作者：
Yun Wu;Delin Chen;Yiwen Hu;Shuqing Zhang;Xinhuai Dong;Hao Liang;Minqi Liang;Yujia Zhu;Chahui Tan;Shu An;Xun Zhu;Jie Yuan;Mengfeng Li;Zhenjian He
生殖系编码模式识别受体（PRRs）在病毒感染过程中识别病原体中常见的分子（病原体相关分子模式[PAMPs]）。这个过程诱导ifn的产生，导致ifn刺激基因的表达，从而建立细胞抗病毒状态来对抗病毒感染。然而，IFN系统的异常激活可能导致免疫病理损伤和系统性自身免疫性疾病，如系统性红斑狼疮。严格控制IFN信号激活对于维持免疫系统的稳态至关重要；然而，其精确调控的机制仍有待阐明。在这项研究中，我们发现锌指蛋白环指蛋白215 （RNF215）在病毒感染的人巨噬细胞中上调。此外，我们证明RNF215至少部分通过与NF-κB亚基p65相互作用抑制I型ifn的产生，并抑制NF-κB在IFNB1启动子区域的积累。此外，我们发现RNF215在系统性红斑狼疮患者中与I型ifn的表达呈负相关，表明RNF215在自身免疫性疾病的发病机制中发挥重要作用。总的来说，我们的数据确定RNF215是I型IFN的关键负调节因子，并表明RNF215是干预异常IFN产生疾病的潜在靶点。RNF215在人巨噬细胞中受病毒感染而上调。RNF215通过阻断NF-κB p65激活抑制IFN-β的产生。SLE患者中RNF215的表达与IFN-β呈负相关。
Germline-encoded pattern recognition receptors (PRRs) recognize molecules frequently found in pathogens (pathogen-associated molecular patterns [PAMPs]) during viral infection. This process induces production of IFNs, leading to expression of IFN-stimulated genes to establish a cellular antiviral state against viral infection. However, aberrant activation of the IFN system may cause immunopathological damage and systemic autoimmune diseases such as systemic lupus erythematosus. Stringent control of IFN signaling activation is critical for maintaining homoeostasis of the immune system; yet, the mechanisms responsible for its precise regulation remain to be elucidated. In this study, we identified that ring finger protein 215 (RNF215), a zinc finger protein, was upregulated by viral infection in human macrophages. In addition, we demonstrated that RNF215 inhibited the production of type I IFNs at least in part via interacting with p65, a subunit of NF-κB, and repressed the accumulation of NF-κB in the promoter region of IFNB1. Moreover, we found that the expression of RNF215 negatively correlated with type I IFNs in patients with systemic lupus erythematosus, indicating that RNF215 plays an important role in the pathogenesis of autoimmune diseases. Collectively, our data identified RNF215 as a key negative regulator of type I IFNs and suggested RNF215 as a potential target for intervention in diseases with aberrant IFN production. Visual Abstract Key Points RNF215 is upregulated by viral infection in human macrophages. RNF215 inhibits the production of IFN-β via blocking NF-κB p65 activation. The expression of RNF215 is negatively correlated with IFN-β in patients with SLE.
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影响因子：
24.1
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