Dupilumab, approved for severe eosinophilic asthma and atopic dermatitis, targets which interleukin receptor subunit, and what is its mechanism of action on Type 2 immunity?

• A Targets the shared IL-4 receptor alpha (IL-4Rα) subunit, blocking both IL-4 and IL-13 signaling simultaneously and reducing JAK1/TYK2-mediated STAT6 activation driving Type 2 inflammation ✓
• B Targets IL-5 receptor alpha, directly eliminating circulating eosinophils
• C Targets IgE Fc receptor (FcεRI) on mast cells, preventing IgE-mediated degranulation
• D Targets TSLP (thymic stromal lymphopoietin) receptor, preventing the upstream epithelial cytokine trigger

Explanation

Dupilumab is a fully human monoclonal antibody targeting IL-4Rα (the alpha subunit of the IL-4 receptor), which is shared between the IL-4 receptor complex (IL-4Rα/γc) and the IL-13 receptor complex (IL-4Rα/IL-13Rα1). By blocking this common subunit, dupilumab simultaneously inhibits both IL-4 and IL-13 signaling, reducing STAT6-mediated Type 2 inflammation (eosinophil recruitment, IgE class switching, mucus production, goblet cell hyperplasia, airway hyperresponsiveness). This dual blockade distinguishes dupilumab from agents targeting only IL-5 (mepolizumab, reslizumab) or only IL-13 (tralokinumab). Omalizumab targets IgE; tezepelumab targets TSLP.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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Written and medically reviewed by the StethoPrep medical team.