Dupilumab: Advances in the off‐label usage ofIL4/IL13antagonist in dermatoses

Type 2 immune response refers to a complicated series of immune responses characterized by Th2 polarization and Th2 cytokines secretion. The IgE secretion, airway hypersensitivity, and effector cell recruitment (eosinophils, mast cells, basophils) in skin lesion and peripheral blood stream could be upregulated during the activation of type 2 immune response. Th1/Th2 ratio, also referred as Th1/Th2 balance, represent the T lymphocytes immune pattern to a certain degree: Th1-dominated responses are often involved in intracellular infections (e.g., mycobacterium tuberculosis) and autoimmune diseases (e.g., Graves' disease) while Th2-dominated responses are involved in allergic conditions (e.g., atopic dermatitis, eczema), IgE mediated diseases (e.g., urticaria), and fibrotic dermatoses (e.g., keloids). Dupilumab, as one of the most widely applied Th2 cytokine inhibitors, could block the bioactivity of IL-14/IL-13 via competitively binding to the common IL-4Rα subunit shared by IL-4 and IL-13 receptors. In addition to the direct inhibition of type 2 response, dupilumab is also effective in autoimmune and some infectious skin diseases through indirect regulation of type 1 immune response. The pathological mechanism of Th2 responses and advanced clinical application of dupilumab in skin diseases will be summarized and discussed in the review.