Eosinophil Subtypes-specific miRNA Expression Changes and Their Impact on Target Genes in Asthma

Introduction MicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression at the post-transcriptional level. In the context of allergic asthma (AA), several miRNAs have been found to exhibit differential expression in eosinophils; however no data about eosinophil subtypes-specific miRNAs and their mediated regulation of target genes are known so far Aim To investigate the changes of selected miRNA-target genes (PRG2,CYSTLR1,RANTES,IL-1β) in lung-resident-like eosinophils (rEOS)-like and inflammatory-like eosinophils (iEOS)-like cells in AA patients Methods We studied 12 AA patients and 16 healthy subjects (HS). Total blood eosinophils were isolated by high-density centrifugation and magnetic separation, phenotyping–with magnetic beads conjugated antibodies against CD62L. The expression of miRNAs and their target genes in eosinophils was measured by RT-qPCR Results In the AA group,miR-146b-5p increased and its target gene RANTES decreased in iEOS-like cells compared to HS, p<0.05. Asthmatic individuals showed elevated miR-185-5p expression in both eosinophil subtypes,along with decreased CYSTLR1 expression, p<0.05. Additionally,another target gene,PRG2,expression specifically decreased in rEOS-like cells, p<0.05. Furthermore,in the AA group,miR-21-5p decreased in iEOS-like cells compared to HS (p<0.05),while IL-1β expression remained unchanged. Moreover, comparing iEOS-like cells and rEOS-like cells within the AA group,IL-1β expression increased in iEOS-like cells, p<0.05 Conclusions The study revealed that eosinophil subtype-specific miRNA expression changes in AA patients may influence the regulation of their target genes, elucidating the biological differences among eosinophil subtypes