Interleukin-4 receptor alpha (IL-4Rα) containing complexes (IL-4Rα)

The Interleukin-4 receptor alpha (IL-4Rα) is a critical signaling component of the interleukin-4 (IL-4) and interleukin-13 (IL-13) receptor systems, which are central to the Type 2 (Th2) immune response [1.3.1, 1.5.1]. It functions as a shared subunit in two distinct heterodimeric complexes: the Type I receptor (comprising IL-4Rα and the common gamma chain) and the Type II receptor (comprising IL-4Rα and IL-13Rα1) [1.3.3, 1.5.2]. The Type I complex specifically binds IL-4, while the Type II complex can be activated by both IL-4 and IL-13 [1.3.2, 1.3.5]. Upon ligand binding, these complexes initiate intracellular signaling primarily through the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway, specifically activating STAT6 [1.1.1, 1.3.3]. This signaling cascade drives essential immune processes such as B-cell class switching to IgE, Th2 cell differentiation, and the alternative activation of macrophages (M2 polarization) [1.3.1, 1.3.2]. Dysregulation or overactivation of IL-4Rα-mediated signaling is a primary driver of allergic and inflammatory diseases, including atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyps [1.2.3, 1.4.1]. In the context of oncology, aberrant IL-4Rα signaling has been implicated in promoting a pro-tumorigenic microenvironment and enhancing cancer cell survival [1.3.1, 1.5.1]. Therapeutic targeting of IL-4Rα, most notably with the monoclonal antibody dupilumab, allows for the simultaneous inhibition of IL-4 and IL-13 signaling [1.1.1, 1.4.2]. This dual blockade has proven highly effective in reducing chronic Th2-mediated inflammation and is a cornerstone of modern treatment for moderate-to-severe atopic diseases [1.2.3, 1.4.1].

Other names

CD124IL4RAInterleukin-4 receptor subunit alphaIL-4R alphaType I IL-4 receptorType II IL-4 receptor

IL-4Rα antagonists bind to the alpha subunit of the interleukin-4 receptor, preventing the assembly of Type I (IL-4Rα/γc) and Type II (IL-4Rα/IL-13Rα1) receptor complexes [1.1.1, 1.3.3]. This blockade inhibits the signaling of both IL-4 and IL-13 cytokines, thereby suppressing the JAK-STAT pathway (specifically STAT6 activation) and reducing Th2-mediated inflammatory responses [1.2.3, 1.5.1].