Type II Interleukin-4 receptor complex (Type II IL-4R)

The Type II Interleukin-4 (IL-4) receptor complex is a heterodimeric signaling unit composed of the IL-4 receptor alpha (IL-4Rα) chain and the IL-13 receptor alpha 1 (IL-13Rα1) chain [1, 3]. Unlike the Type I complex, which is specific to IL-4, the Type II complex is activated by both IL-4 and IL-13, making it a critical mediator of Type 2 inflammation [1, 5]. Upon ligand binding, the complex recruits Janus kinases (JAK1, JAK2, or TYK2) to activate the STAT6 signaling pathway, leading to the transcription of genes involved in Th2 cell differentiation and IgE production [3, 7]. This receptor complex is predominantly expressed on non-hematopoietic cells such as epithelial cells, smooth muscle cells, and fibroblasts, as well as some immune cells like myeloid cells [4, 7]. It plays a central role in the pathophysiology of allergic diseases, including asthma, atopic dermatitis, and chronic rhinosinusitis, by promoting airway hyperresponsiveness and tissue remodeling [1, 5, 9]. Therapeutic targeting of this complex, most notably through the monoclonal antibody dupilumab which binds the IL-4Rα subunit, has proven highly effective in treating multiple Th2-mediated inflammatory conditions [6, 8].

Other names

IL-4Rα/IL-13Rα1 complexIL-4/IL-13 receptor complexInterleukin-4 receptor type IIType II IL-4R

Antagonism of IL-4 and IL-13 signaling by blocking the shared IL-4Rα subunit, preventing the formation of the signaling complex and subsequent activation of the JAK/STAT6 pathway.