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MicroRNA-2187 通过靶向 TRAF6 调节鱼类中的 NF-κB 和 IRF3 通路。

MicroRNA-2187 Modulates the NF-κB and IRF3 Pathway in Teleost Fish by Targeting TRAF6.

机构信息

Laboratory of Fish Molecular Immunology, College of Fisheries and Life Science, Shanghai Ocean University, Shanghai, China.

Laboratory of Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China.

出版信息

Front Immunol. 2021 Feb 15;12:647202. doi: 10.3389/fimmu.2021.647202. eCollection 2021.

Abstract

The innate immune organs and cells detect the invasion of pathogenic microorganisms, which trigger the innate immune response. A proper immune response can protect the organisms from pathogen invasion. However, excessive immunity can destroy immune homeostasis, leading to uncontrolled inflammation or pathogen transmission. Evidence shows that the miRNA-mediated immune regulatory network in mammals has had a significant impact, but the antibacterial and antiviral responses involved in miRNAs need to be further studied in lower vertebrates. Here, we report that miR-2187 as a negative regulator playing a critical role in the antiviral and antibacterial response of miiuy croaker. We find that pathogens such as and rhabdoviru (SCRV) can up-regulate the expression of miR-2187. Elevated miR-2187 is capable of reducing the production of inflammatory factors and antiviral genes by targeting TRAF6, thereby avoiding excessive inflammatory response. Furthermore, we proved that miR-2187 modulates innate immunity through TRAF6-mediated NF-κB and IRF3 signaling pathways. The above results indicate that miR-2187 acts as an immune inhibitor involved in host antibacterial and antiviral responses, thus enriching the immune regulatory network of the interaction between host and pathogen in lower vertebrates.

摘要

先天免疫器官和细胞检测到病原微生物的入侵,从而引发先天免疫反应。适当的免疫反应可以保护生物体免受病原体的入侵。然而,过度的免疫反应会破坏免疫平衡,导致不受控制的炎症或病原体传播。有证据表明,哺乳动物中 miRNA 介导的免疫调节网络产生了重大影响,但 miRNA 参与的抗菌和抗病毒反应需要在低等脊椎动物中进一步研究。在这里,我们报告 miR-2187 作为一种负调控因子,在米鱼抗病毒和抗菌反应中发挥关键作用。我们发现,病原体如 和弹状病毒(SCRV)可以上调 miR-2187 的表达。升高的 miR-2187 能够通过靶向 TRAF6 减少炎症因子和抗病毒基因的产生,从而避免过度的炎症反应。此外,我们证明 miR-2187 通过 TRAF6 介导的 NF-κB 和 IRF3 信号通路来调节先天免疫。上述结果表明,miR-2187 作为一种参与宿主抗菌和抗病毒反应的免疫抑制剂,丰富了宿主与病原体相互作用中低等脊椎动物的免疫调节网络。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95cc/7917119/c864691a6953/fimmu-12-647202-g0001.jpg

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