Drosophila Relish‐mediated miR‐317 expression facilitates immune homeostasis restoration via inhibiting PGRP‐LC
Drosophila Relish‐mediated miR‐317 expression facilitates immune homeostasis restoration via inhibiting PGRP‐LC
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DOI：
10.1002/eji.202250034
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发表时间：
2022-09
影响因子：
5.4
通讯作者：
Hongjian Zhou;Shanshan Wu;Li Liu;Xiaoqi Liu;Siyu Lan;Jiajun Jiang;Wan Yang;P. Jin;X. Xia;Fei Ma
中科院分区：
文献类型：
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作者：
Hongjian Zhou;Shanshan Wu;Li Liu;Xiaoqi Liu;Siyu Lan;Jiajun Jiang;Wan Yang;P. Jin;X. Xia;Fei Ma
先天免疫是抵抗病原体的第一道也是必不可少的防线，需要严格调节免疫强度和持续时间，以平衡过度或不足的免疫反应。 MicroRNA (miRNA) 是果蝇免疫反应的重要调节因子，但免疫相关 miRNA 的调节方式仍知之甚少。在此，我们阐明了 miR-317 参与 NF-κB 转录因子 Relish 介导的果蝇 Imd 通路响应革兰氏阴性 (G-) 细菌刺激。值得注意的是，免疫反应的动态表达谱表明，Relish 同时增强了效应抗菌肽 Dpt 以及感染后 miR-317 的表达。上调miR-317可以进一步下调PGRP-LC的表达，从而在果蝇Imd通路中形成反馈，防止过度激活并恢复免疫稳态。总而言之，我们的研究不仅揭示了一种新的 Relish/miR-317/PGRP-LC 调节轴来减弱果蝇 Imd 免疫反应并促进免疫稳态恢复，而且还为动物先天免疫调节的复杂机制提供了重要的见解。
Innate immunity is the first and essential line for resisting pathogens, and the immune intensity and duration need to be strictly regulated to balance excessive or insufficient immune response. MicroRNAs (miRNAs) are crucial regulators of immune response in Drosophila, yet how immune‐related miRNAs are regulated remains poorly understood. Herein, we elucidated that the involvement of miR‐317 in NF‐κB transcription factor Relish mediated Drosophila Imd pathway in response to Gram‐negative (G‐) bacteria stimulation. Remarkably, the dynamic expression profiling for immune response indicated that Relish simultaneously enhances the expression of the effector antimicrobial peptide Dpt as well as miR‐317 post‐infection. Upregulation of miR‐317 could further down‐regulate the expression of PGRP‐LC, thereby forming a feedback in Drosophila Imd pathway to prevent over‐activation and restore immune homeostasis. Taken together, our study not only uncovers a novel Relish/miR‐317/PGRP‐LC regulatory axis to attenuate Drosophila Imd immune response and facilitate immune homeostasis restoration, but also provides vital insights into the complex mechanisms of animal innate immune regulation.