Dupilumab is approved for severe eosinophilic/type 2 asthma. Its mechanism involves blocking the receptor shared by IL-4 and IL-13. This shared receptor subunit is:

• A JAK1, which is the intracellular tyrosine kinase activated by both IL-4 and IL-13 receptor complexes
• B STAT6 transcription factor that is phosphorylated downstream of both IL-4 and IL-13 signaling
• C IL-13Ralpha1, the obligate co-receptor that dimerizes with IL-4Ralpha for both cytokine responses
• D IL-4Ralpha (IL-4 receptor alpha chain), which is the common component of both type I (IL-4Ralpha + gamma-c) and type II (IL-4Ralpha + IL-13Ralpha1) receptor complexes ✓

Explanation

Dupilumab is a fully human monoclonal antibody that binds the IL-4Ralpha (IL-4 receptor alpha subunit). IL-4Ralpha is shared between both the type I receptor (IL-4Ralpha + common gamma chain; expressed on T cells and mast cells, mediates IL-4 effects) and the type II receptor (IL-4Ralpha + IL-13Ralpha1; expressed on non-hematopoietic cells including airway epithelium, smooth muscle, goblet cells, mediates both IL-4 and IL-13 effects). By blocking IL-4Ralpha, dupilumab simultaneously inhibits IL-4 and IL-13 signaling, reducing Th2 skewing, IgE class switching, mucus production, and goblet cell hyperplasia. STAT6 is a downstream intracellular mediator, not the target.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.