Chicken miR-126-5p negatively regulates antiviral innate immunity by targeting TRAF3.
Chicken miR-126-5p negatively regulates antiviral innate immunity by targeting TRAF3.
复制标题
鸡miR-126-5p通过靶向TRAF3负向调节抗病毒先天免疫
DOI：
10.1186/s13567-022-01098-x
复制
发表时间：
2022-10-12
影响因子：
4.4
通讯作者：
中科院分区：
文献类型：
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作者：
天然免疫在防止病原微生物入侵方面起着至关重要的作用。然而，先天免疫是一把双刃剑，其过度激活不利于免疫稳态，甚至导致感染宿主的“细胞因子风暴”。宿主发展了一系列负调节机制来平衡免疫反应。本文报道了一种由miRNA介导的鸡先天免疫负调控机制。在GEO数据库中，我们发现miR-126- 5 p在RNA病毒感染的鸡中显著上调。然后通过细胞模型和体内测试进一步显示RNA病毒对miR-126- 5 p的上调。过表达miR-126- 5 p可显著抑制RNA病毒诱导的干扰素和炎症相关基因的表达。在miR-126- 5 p表达被敲低后，实现了相反的结果。生物信息学分析确定TRAF 3为miR-126- 5 p的候选靶基因。实验上，miR-126- 5 p可以靶向TRAF 3，如通过miR-126- 5 p对TRAF 3的内源性表达的影响以及通过TRAF 3 3 'UTR驱动的荧光素酶报告基因测定所示。此外，我们证明了miR-126- 5 p通过阻断MAVS-TRAF 3-TBK 1轴来负调节先天免疫。总之，我们的研究结果表明miR-126- 5 p参与了鸡先天免疫的负调节，可能有助于维持免疫平衡。在线版本包含补充材料，可通过10.1186/s13567-022-01098-x获得。
Innate immunity plays an essential role in preventing the invasion of pathogenic microorganisms. However, innate immunity is a double-edged sword, whose excessive activation is detrimental to immune homeostasis and even leads to a “cytokine storm” of the infected host. The host develops a series of negative regulatory mechanisms to balance the immune response. Here, we report a negative regulatory mechanism of chicken innate immunity mediated by miRNA. In the GEO database, we found that miR-126-5p was markedly up-regulated in chickens infected by RNA viruses. Upregulation of miR-126-5p by RNA virus was then further shown via both a cell model and in vivo tests. Overexpression of miR-126-5p significantly inhibited the expression of interferon and inflammatory cytokine-related genes induced by RNA viruses. The opposite result was achieved after the knockdown of miR-126-5p expression. Bioinformatics analysis identified TRAF3 as candidate target gene of miR-126-5p. Experimentally, miR-126-5p can target TRAF3, as shown by the effects of miR-126-5p on the endogenous expression of TRAF3, and by the TRAF3 3'UTR driven luciferase reporter assay. Furthermore, we demonstrated that miR-126-5p negatively regulated innate immunity by blocking the MAVS-TRAF3-TBK1 axis, with a co-expression assay. Overall, our results suggest that miR-126-5p is involved in the negative regulation of chicken innate immunity, which might contribute to maintaining immune balance. The online version contains supplementary material available at 10.1186/s13567-022-01098-x.
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DOI：
10.1038/nri3665
发表时间：
2014-05
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
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影响因子：
30.5
作者：
通讯作者：
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番鸭视黄酸诱导基因 I (MdRIG-I) 在针对 H9N2 禽流感病毒 (AIV) 感染的先天免疫中发挥作用
影响因子：
1.8
作者：
Cheng, Yuqiang;Huang, Qingqing;Sun, Jianhe
通讯作者：
Sun, Jianhe
影响因子：
30.5
作者：
Kawai, T;Takahashi, K;Akira, S
通讯作者：
Akira, S
影响因子：
3
作者：
Huang B;Qi ZT;Xu Z;Nie P
通讯作者：
Nie P