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诱饵蛋白 Decoys Dif/Dorsal 减少抗菌肽产物,有助于恢复 Toll 免疫稳态。

Decoys Dif/Dorsal to Reduce Antimicrobial Peptide Products for Restoring Toll Immunity Homeostasis.

机构信息

Laboratory for Comparative Genomics and Bioinformatics & Jiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Science, Nanjing Normal University, Nanjing 210046, China.

Jiangsu Provincial Key Construction Laboratory of Special Biomass Byproduct Resource Utilization, School of Food Science, Nanjing Xiaozhuang University, Nanjing 211171, China.

出版信息

Int J Mol Sci. 2021 Sep 18;22(18):10117. doi: 10.3390/ijms221810117.

Abstract

Avoiding excessive or insufficient immune responses and maintaining homeostasis are critical for animal survival. Although many positive or negative modulators involved in immune responses have been identified, little has been reported to date concerning whether the long non-coding RNA (lncRNA) can regulate immunity response. In this study, we firstly discover that the overexpression of can inhibit the expressions of antimicrobial peptides () and () in vivo, thereby suppressing the Toll signaling pathway. Secondly, our results demonstrate that can interact with transcription factors Dif/Dorsal in the nucleus based on both subcellular localization and RIP analyses. Thirdly, our findings reveal that can decoy Dif/Dorsal away from the promoters of and to repress their transcriptions by ChIP-qPCR and dual luciferase report experiments. Fourthly, the dynamic expression changes of , , and in wild-type flies () at different time points after stimulation disclose that can help restore immune homeostasis in the later period of immune response. Overall, our study reveals a novel mechanism by which serves as a Dif/Dorsal decoy to downregulate antimicrobial peptide expressions for restoring Toll immunity homeostasis, and provides a new insight into further studying the complex regulatory mechanism of animal innate immunity.

摘要

避免过度或不足的免疫反应并维持体内平衡对于动物的生存至关重要。尽管已经鉴定出许多参与免疫反应的正向或负向调节剂,但迄今为止,关于长链非编码 RNA (lncRNA) 是否可以调节免疫反应的报道很少。在这项研究中,我们首先发现过表达 可以在体内抑制抗菌肽 () 和 () 的表达,从而抑制 Toll 信号通路。其次,我们的结果表明,基于亚细胞定位和 RIP 分析, 可以在核内与转录因子 Dif/Dorsal 相互作用。第三,我们的发现表明,通过 ChIP-qPCR 和双荧光素酶报告实验, 可以将 Dif/Dorsal 诱捕到 和 的启动子之外,从而抑制它们的转录。第四,在 刺激后不同时间点的野生型果蝇 () 中 、 、 和 的动态表达变化表明, 可以帮助 在免疫反应后期恢复免疫稳态。总的来说,我们的研究揭示了一种新的机制,即 作为 Dif/Dorsal 的诱饵,下调抗菌肽的表达,以恢复 Toll 免疫稳态,为进一步研究动物先天免疫的复杂调控机制提供了新的视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1dd2/8468853/b00c4a6e791e/ijms-22-10117-g001.jpg

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