Interleukin-4 receptor alpha – Type II receptor complex (IL-4Rα/IL-13Rα1)

The Interleukin-4 receptor alpha – Type II receptor complex is a heterodimeric cytokine receptor composed of the Interleukin-4 receptor alpha (IL-4Rα) and the Interleukin-13 receptor alpha 1 (IL-13Rα1) subunits [1, 3]. It serves as a functional signaling unit for both Interleukin-4 (IL-4) and Interleukin-13 (IL-13), which are key drivers of Type 2 (Th2) inflammation [7, 8]. Upon ligand binding, the complex activates the Janus kinase (JAK)/Signal Transducer and Activator of Transcription 6 (STAT6) pathway, leading to downstream effects such as IgE class switching in B cells, mucus hypersecretion, and recruitment of eosinophils [5, 15]. This receptor complex is predominantly expressed on non-hematopoietic cells like epithelial cells, smooth muscle cells, and fibroblasts, making it a critical mediator of tissue-level allergic responses and remodeling [7, 8]. Therapeutic targeting of this complex, most notably through the IL-4Rα-binding monoclonal antibody dupilumab, has proven highly effective in treating chronic inflammatory conditions such as asthma, atopic dermatitis, and eosinophilic esophagitis [2, 6, 13]. By blocking the shared IL-4Rα subunit, these therapies simultaneously inhibit the signaling of both IL-4 and IL-13, addressing the underlying pathophysiology of multiple comorbid allergic diseases [8, 15].

Other names

Type II IL-4 receptorIL-4Rα/IL-13Rα1 complexInterleukin-4 receptor type IIIL-4R type IIIL-4Rα/IL-13Rα1 heterodimer

Inhibition of IL-4 and IL-13 signaling by binding to the IL-4Rα subunit, preventing the formation of the active signaling complex and subsequent activation of the JAK/STAT6 pathway [2, 8, 15].