Drosophila Myc (dMyc), as a broad-spectrum transcription factor, can regulate the expression of a large number of genes to control diverse cellular processes, such as cell cycle progression, cell growth, proliferation and apoptosis. However, it remains largely unknown about whether dMyc can be involved in Drosophila innate immune response. Here, we have identified dMyc to be a negative regulator of Drosophila Imd pathway via the loss- and gain-of-function screening. We demonstrate that dMyc inhibits Drosophila Imd immune response via directly activating miR-277 transcription, which further inhibit the expression of imd and Tab2-Ra/b. Importantly, dMyc can improve the survival of flies upon infection, suggesting inhibiting Drosophila Imd pathway by dMyc is vital to restore immune homeostasis that is essential for survival. Taken together, our study not only reports a new dMyc-miR-277-imd/Tab2 axis involved in the negative regulation of Drosophila Imd pathway, and provides a new insight into the complex regulatory mechanism of Drosophila innate immune homeostasis maintenance.

果蝇Myc（dMyc）作为一种广谱转录因子，可以调节大量基因的表达，从而控制多种细胞过程，例如细胞周期进程，细胞生长，增殖和凋亡。但是，关于dMyc是否可参与果蝇先天免疫应答的认识仍很未知。在这里，我们已经通过功能丧失和获得功能筛选确定了dMyc是果蝇Imd途径的负调节剂。我们证明dMyc通过直接激活miR-277转录抑制果蝇Imd免疫反应，从而进一步抑制imd和Tab2-Ra / b的表达。重要的是，dMyc可以提高感染时苍蝇的存活率，这表明dMyc抑制果蝇Imd途径对于恢复生存所必需的免疫稳态是至关重要的。综上所述，我们的研究不仅报道了涉及果蝇Imd途径负调控的新dMyc-miR-277-imd / Tab2轴，而且为果蝇固有免疫稳态的复杂调控机制提供了新见解。