Dupilumab

Type 2 inflammatory processes in various allergic and atopic conditions, such as asthma and atopic diseases, involve the type 2 helper T-cell (Th2) immunity. Upregulation of this Type 2/Th2 pathway is commonly observed in other inflammatory conditions and the activation of Th2 cells is linked to the production of Th2-associated cytokines, such as interleukin (IL) 4, IL-5, IL-9, and IL-13. IL-4 and IL-13 play a central role in inducing inflammatory conditions such as allergic rhinitis, asthma, and atopic dermatitis, by regulating Type 2 inflammation and immune function. These inflammatory cytokines work by modulating gene expression downstream of receptor signalling, regulating Th2 cell differentiation, and activating inflammatory cells such as mast cells and macrophages.

There are two types of receptors for IL-4: the type 1 receptor, which is composed of the IL-4 chain (IL-4Rα) and a γ chain (γC), and the type 2 receptor, which is composed of the IL-4Rα chain and the α1 chain of the IL-13 receptor (IL-13Rα1). Essentially, IL‐4Rα is a component shared by the IL‐4 and IL-13 receptor complexes and is ubiquitously expressed on both innate and adaptive immune cells to promote the signaling of IL-4 and IL-13. The type I receptor is primarily expressed on lymphocytes and controls Th2-cell differentiation, whereas the type II receptor is mostly found across resident and myeloid cells. Dupilumab is a fully human monoclonal antibody directed against IL‐4Rα to inhibit the signalling of IL‐4 and IL‐13. Dupilumab inhibits IL-4 signalling via the Type I receptor (IL-4Rα/γc), and both IL-4 and IL-13 signaling through the Type II receptor (IL-4Rα/IL-13Rα). It ultimately downregulates type-2 immunity.