The Relish/miR-275/Dredd mediated negative feedback loop is crucial to restoring immune homeostasis of Drosophila Imd pathway
The Relish/miR-275/Dredd mediated negative feedback loop is crucial to restoring immune homeostasis of Drosophila Imd pathway
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DOI：
10.1016/j.ibmb.2023.104013
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发表时间：
2023-10-11
影响因子：
3.8
通讯作者：
Ma，Fei
中科院分区：
文献类型：
--
作者：
Pan，Wanwan;Yao，Xiaolong;Ma，Fei
The NF-κB/Relish, as a core transcription factor ofDrosophilaimmune deficiency (Imd) pathway, activates the transcriptions of antimicrobial peptides (AMPs) to combat gram-negative bacterial infections, but its role in regulating miRNA expression during immune response has less been reported. We here describe a negative feedback loop of Imd signaling mediated by Relish/miR-275/Dreddthat controlsDrosophilaimmune homeostasis afterEscherichia coli(E.coli) infection. Our results demonstrate that Relish may directly activate the transcription of miR-275 via binding to its promoter invitroandvivo, particularly miR-275 further inhibits the expression ofDreddthrough binding to its 3′UTR to negatively controlDrosophilaImd immune response. Remarkably, the ectopic expression of miR-275 significantly reducesDrosophilalifespan. More importantly, our work uncovers a new mechanism by which Relish can flexibly switch its role to maintainDrosophilaimmune response and homeostasis during infection. Collectively, our study not only reveals the functional duality of Relish in regulating immune response ofDrosophilaImd pathway, but also provides a new insight into the maintenance of animal innate immune homeostasis.
