Type 2 interleukin-4 receptor (Type 2 IL-4R)

The Type 2 interleukin-4 receptor (Type 2 IL-4R) is a heterodimeric protein complex composed of the interleukin-4 receptor alpha (IL-4Rα) chain and the interleukin-13 receptor alpha 1 (IL-13Rα1) chain (UniProt P24394, P78552). Unlike the Type 1 receptor, which is specific to IL-4, the Type 2 receptor serves as a functional signaling unit for both IL-4 and IL-13, two key cytokines driving Type 2 (Th2) inflammation (PubMed: 10446022). It is widely expressed on non-hematopoietic cells such as airway epithelial cells, smooth muscle cells, and fibroblasts, as well as on various immune cells (StatPearls: NBK538201). Upon ligand binding, the receptor activates the JAK/STAT signaling pathway, primarily through STAT6, leading to physiological changes like mucus overproduction, tissue remodeling, and IgE synthesis (PubMed: 29307919). Because of its central role in allergic and inflammatory pathways, the Type 2 IL-4R is a major therapeutic target for conditions like moderate-to-severe asthma and atopic dermatitis (PubMed: 32103417). Drugs like dupilumab target the shared IL-4Rα subunit, effectively inhibiting the signaling of both IL-4 and IL-13 through this receptor complex (FDA: Dupixent Label).

Other names

IL-4Rα/IL-13Rα1 complexInterleukin-4 receptor type IIIL-4/IL-13 receptorType II IL-4 receptor

Monoclonal antibody antagonist that binds to the IL-4Rα subunit, inhibiting the signaling of both IL-4 and IL-13 through the Type 2 receptor complex.