AUTHOR=He Yan , Liu Yuting , Yang Yuyue , Liu Yang , Jia Xuewen , Shen Yubang , Xu Xiaoyan , Li Jiale 

TITLE=elk1/miR-462-731 Feedback Loop Regulates Macrophages Polarization and Phagocytosis in Grass Carp (Ctenopharyngodon idella)

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.946857

DOI=10.3389/fimmu.2022.946857

ISSN=1664-3224

ABSTRACT=<p>MicroRNA clusters are microRNAs (miRNAs) that are distributed in close proximity on chromosomes. In this study, we report a miRNA cluster identified from grass carp (<italic>Ctenopharyngodon idella</italic>), miR-462-731, which plays a positive role in host antibacterial immunity. The expression of miR-462-731 was disrupted after infection by <italic>Aeromonas hydrophila</italic>. Transcription factor ETS transcription factor ELK1 was identified to bind to the promoter of the miR-462-731 cluster and suppress its expression. In addition, miR-731 negatively regulates the expression of <italic>elk1</italic>, forms an elk1/miR-462-731 double negative feedback loop. In addition, we found that miR-731 directly targets ezrin a (<italic>ezra</italic>), participates in inducing PI3K/AKT signaling in macrophage, to induce macrophage polarization to the M1 phenotype with stronger phagocytosis. Our results demonstrate a novel elk1/miR-462-731 feedback loop. The data deepen our understanding of the relationship between macrophage polarization and phagocytosis in teleost fish.</p>