AUTHOR=Hsu Alan Y. , Wang Tianqi , Syahirah Ramizah , Liu Sheng , Li Kailing , Zhang Weiwei , Wang Jiao , Cao Ziming , Tian Simon , Matosevic Sandro , Staiger Christopher J. , Wan Jun , Deng Qing 

TITLE=Rora Regulates Neutrophil Migration and Activation in Zebrafish

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.756034

DOI=10.3389/fimmu.2022.756034

ISSN=1664-3224

ABSTRACT=<p>Neutrophil migration and activation are essential for defense against pathogens. However, this process may also lead to collateral tissue injury. We used microRNA overexpression as a platform and discovered protein-coding genes that regulate neutrophil migration. Here we show that miR-99 decreased the chemotaxis of zebrafish neutrophils and human neutrophil-like cells. In zebrafish neutrophils, miR-99 directly targets the transcriptional factor <italic>RAR-related orphan receptor alpha (roraa)</italic>. Inhibiting RORα, but not the closely related RORγ, reduced chemotaxis of zebrafish and primary human neutrophils without causing cell death, and increased susceptibility of zebrafish to bacterial infection. Expressing a dominant-negative form of Rorα or disrupting the <italic>roraa</italic> locus specifically in zebrafish neutrophils reduced cell migration. At the transcriptional level, RORα regulates transmembrane signaling receptor activity and protein phosphorylation pathways. Our results, therefore, reveal previously unknown functions of miR-99 and RORα in regulating neutrophil migration and anti-microbial defense.</p>