Evidence for a Role of the Long Non-Coding RNA ITGB2-AS1 in Eosinophil Differentiation and Functions

Eosinophils, a type of granulocyte derived from myeloid precursors in the bone marrow, are distinguished by their cytoplasmic granules. They play crucial roles in immunoregulation, tissue homeostasis, and host defense, while also contributing to the pathogenesis of various inflammatory diseases. Although long non-coding RNAs (lncRNAs) are known to be involved in eosinophilic conditions, their specific expression and functions within eosinophils have not been thoroughly investigated, largely due to the reliance on tissue homogenates. In an effort to address this gap, we analyzed publicly available high-throughput RNA sequencing data to identify lncRNAs associated with eosinophilic conditions. Among the identified lncRNAs, ITGB2 antisense RNA 1 (<i>ITGB2-AS1</i>) was significantly downregulated in blood eosinophils from patients with hypereosinophilia. To further explore its role in eosinophil biology, we generated a stable <i>ITGB2-AS1</i> knockdown in the HL-60 cell line. Interestingly, <i>ITGB2-AS1</i> deficiency led to impaired eosinophil differentiation, as evidenced by a reduction in cytoplasmic granules and decreased expression of key eosinophil granule proteins, including eosinophil peroxidase (EPX) and major basic protein-1 (MBP-1). Additionally, <i>ITGB2-AS1</i>-deficient cells exhibited compromised eosinophil effector functions, with reduced degranulation and impaired production of reactive oxygen species (ROS). These findings suggest that <i>ITGB2-AS1</i> plays a pivotal role in eosinophil differentiation and function, positioning it as a novel regulator in eosinophil biology.