Interleukin-4 receptor complex (IL-4R)

The Interleukin-4 receptor (IL-4R) complex is a transmembrane protein assembly essential for mediating the biological effects of interleukin-4 (IL-4) and interleukin-13 (IL-13), which are key drivers of Type 2 inflammation (UniProt P24394; PubMed: 30110519). The complex exists in two configurations: the Type I receptor, found mainly on hematopoietic cells, consists of the IL-4R alpha subunit and the common gamma chain (gc); the Type II receptor, found on both hematopoietic and non-hematopoietic cells, consists of IL-4R alpha and the IL-13R alpha 1 subunit (StatPearls: NBK538210). Upon ligand binding, the receptor activates Janus kinases (JAK1, JAK2, or JAK3) and the Signal Transducer and Activator of Transcription 6 (STAT6), leading to the expression of genes involved in B-cell IgE isotype switching and Th2 cell differentiation (PubMed: 29307232). Overactivation of this pathway is central to the pathophysiology of allergic and atopic diseases, including asthma, atopic dermatitis, and eosinophilic esophagitis (PubMed: 31607506). Pharmacological intervention typically targets the IL-4R alpha subunit, which is common to both receptor types, to inhibit the dual signaling of IL-4 and IL-13. Dupilumab, a prominent monoclonal antibody targeting IL-4R alpha, has demonstrated significant clinical efficacy in reducing inflammatory symptoms and exacerbations in patients with chronic Type 2 inflammatory conditions (FDA: Dupixent Label).

Other names

IL-4 receptorCD124Interleukin-4 receptor subunit alphaIL4RAType I interleukin-4 receptorType II interleukin-4 receptor

Antagonist of the IL-4R alpha subunit, which prevents the formation of both Type I and Type II receptor complexes, thereby blocking the signaling of IL-4 and IL-13 cytokines (PubMed: 30110519).