Interleukin-5 receptor subunit alpha (IL-5RA) (IL-5RA)

The Interleukin-5 receptor subunit alpha (IL-5RA), also known as CD125, is a type I cytokine receptor that serves as the specific binding component for Interleukin-5 (IL-5) [1, 4]. It is primarily expressed on eosinophils and basophils, playing a pivotal role in their differentiation, activation, and survival [3]. The intracellular signaling domain of IL-5RA is critical for recruiting and activating Janus kinase 2 (JAK2), which subsequently triggers the STAT5, MAPK, and PI3K signaling pathways [3]. Dysregulation of these pathways is a hallmark of eosinophilic inflammatory diseases, such as severe eosinophilic asthma and hypereosinophilic syndrome [3, 5]. Therapeutic intervention typically involves monoclonal antibodies like benralizumab, which binds to the extracellular portion of IL-5RA to block ligand interaction and induce eosinophil apoptosis via antibody-dependent cell-mediated cytotoxicity (ADCC) [2, 5]. While the intracellular domain itself is not currently targeted by specific small molecules in clinical use, it remains a vital area of study for understanding cytokine-mediated signal transduction and eosinophil biology [1, 3].

Other names

CD125IL5RIL5RAInterleukin-5 receptor alpha chainHSIL5R3

Benralizumab is a humanized monoclonal antibody that binds to the alpha subunit of the interleukin-5 receptor (IL-5RA) on the surface of eosinophils and basophils. This binding prevents IL-5 from interacting with its receptor, thereby inhibiting the signaling required for eosinophil maturation and survival. Additionally, the Fc portion of the antibody (which is afucosylated) binds to the FcγRIIIa receptor on natural killer (NK) cells, triggering antibody-dependent cell-mediated cytotoxicity (ADCC) and leading to the rapid depletion of eosinophils [2, 5].