转录因子Relish调控microRNA表达参与果蝇Imd通路免疫响应的机制研究

Relish(Rel)调控抗菌肽表达在果蝇Imd通路免疫防御革兰氏阴性菌的侵染中起关键作用。然而，Rel作为转录因子是否也能调节microRNA（miRNA）表达参与果蝇Imd免疫响应至今仍较少涉及。申请人前期多组学分析发现Rel能正或负调节miRNA表达，提示Rel调节miRNA表达参与了果蝇Imd免疫响应。因此，为深刻揭示Rel调控miRNA表达在果蝇Imd免疫响应中的功能机制，本课题将利用ChIP技术鉴定Rel调控的miRNA；实验验证Rel对miRNA以及miRNA对靶基因的调控；重点研究Rel调节的miRNA靶向抗菌肽、激活子（如Sick）、抑制子（如Caspar）等在Imd免疫响应中的功能，阐明Rel调节miRNA表达在果蝇Imd免疫响应中的作用机制。课题的预期研究成果对全面完善果蝇免疫稳态维持机制的研究和阐明动物先天免疫响应的复杂分子机制都具有重要的理论意义。

The Relish (Rel) regulating expressions of antimicrobial peptide genes plays a key role in immune defense of Drosophila Imd signal pathway against Gram negative bacteria invasion. However, whether the Rel, as a transcription factor, can also regulate microRNA (miRNA) expressions to participate in Drosophila Imd pathway immune response, which is still rarely studied. Our previous multi-omics analyses have found that the Rel could positively or negatively regulate expressions of many miRNAs, suggesting that the Rel should regulate miRNA expression and participate in the immune response of Drosophila Imd pathway. Therefore, in order to further uncover the functional mechanism of the Rel regulating miRNA expressions involved in Drosophila Imd immune response, we will use the ChIP technique to identify these miRNAs regulated by the Rel. We will also validate Rel targeting miRNAs and miRNA regulating target genes in vivo and in vitro in this study. And that we will further study the functions of Rel regulating miRNA to control expressions of antimicrobial peptide genes, activator (Sick) and inhibitor (Caspar) of Drosophila Imd pathway in vivo and in vitro, revealing the mechanism of Rel regulating miRNA expression involved in innate immune response of Drosophila Imd pathway. Taken together，the completion of the study is of great theoretical significance for comprehensively improving the study on mechanisms of maintaining innate immune homeostasis in Drosophila melanogaster and illuminating the complex regulatory mechanism of animal innate immune response.