Long noncoding RNA IDI2-AS1 modulates the expression of interleukin 5 in human cells

Long noncoding RNAs (lncRNAs) have emerged as critical regulators of gene expression, influencing a wide range of biological processes. In this study, we investigate the regulatory role of the lncRNA IDI2-AS1 in the immune response. Our previous observations demonstrated that IDI2-AS1 expression is downregulated in A549 cells upon exposure to lipopolysaccharide (LPS) and poly I:C, which mimic bacterial and viral infections, respectively. Here, we analyzed the expression changes of 13 immune response genes following siRNA-mediated knockdown of IDI2-AS1 in A549 cells. Notably, our results revealed a significant and selective upregulation of interleukin 5 (IL5) mRNA expression, which increased approximately 60-fold, along with a corresponding ∼70-fold increase in IL5 protein levels. These findings suggest a novel regulatory mechanism in which IDI2-AS1 functions as a suppressor of IL5 expression under normal conditions. During simulated bacterial or viral infections, the downregulation of IDI2-AS1 appears to initiate a rapid and robust increase in IL5 expression. Given the pivotal role of IL5 in allergic inflammation and eosinophil regulation, the IDI2-AS1-IL5 axis may represent an important pathway in the immune response to pathogenic challenges. This study provides new insights into the intricate interplay between lncRNAs and cytokine gene regulation in innate immunity, potentially offering novel therapeutic targets for immune-related disorders.