Henan Key Laboratory of immunology and targeted drug, Xinxiang Medical University, Xinxiang, Henan Province, China.
Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, Henan Province, China.
PLoS Pathog. 2020 Mar 3;16(3):e1008387. doi: 10.1371/journal.ppat.1008387. eCollection 2020 Mar.
Mediator of IRF3 activation (MITA, also named as STING/ERIS/MPYS/TMEM173), is essential to DNA virus- or cytosolic DNA-triggered innate immune responses. In this study, we demonstrated the negative regulatory role of RING-finger protein (RNF) 90 in innate immune responses targeting MITA. RNF90 promoted K48-linked ubiquitination of MITA and its proteasome-dependent degradation. Overexpression of RNF90 inhibited HSV-1- or cytosolic DNA-induced immune responses whereas RNF90 knockdown had the opposite effects. Moreover, RNF90-deficient bone marrow-derived dendritic cells (BMDCs), bone marrow-derived macrophages (BMMs) and mouse embryonic fibroblasts (MEFs) exhibited increased DNA virus- or cytosolic DNA-triggered signaling and RNF90 deficiency protected mice from DNA virus infection. Taken together, our findings suggested a novel function of RNF90 in innate immunity.
IRF3 激活介质（MITA，也称为 STING/ERIS/MPYS/TMEM173）对于 DNA 病毒或细胞质 DNA 触发的先天免疫反应至关重要。在这项研究中，我们证明了 RING 指蛋白（RNF）90 在针对 MITA 的先天免疫反应中的负调控作用。RNF90 促进 MITA 的 K48 连接泛素化及其蛋白酶体依赖性降解。RNF90 的过表达抑制 HSV-1 或细胞质 DNA 诱导的免疫反应，而 RNF90 的敲低则产生相反的效果。此外，RNF90 缺陷型骨髓来源树突状细胞（BMDCs）、骨髓来源巨噬细胞（BMMs）和小鼠胚胎成纤维细胞（MEFs）表现出增强的 DNA 病毒或细胞质 DNA 触发的信号转导，而 RNF90 缺陷型可保护小鼠免受 DNA 病毒感染。总之，我们的研究结果表明 RNF90 在先天免疫中具有新的功能。
