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Figure 1. Legend.
Mechanisms of action of type-2 immunity targeting biologicals . 1. Omalizumab binds to soluble IgE released from B-cells, reducing the quantity of free IgE available to bind to FcεRI on basophils, mast cells and eosinophils, reducing IgE cross-linking. A reduction of free soluble IgE also downregulates FcεRI expression on the surface on the surface of effector cells. Moreover, the paucity of available IgE reduces IgE-CD23 interactions on B-cells, reducing Th2 differentiation and IgE synthesis. Omalizumab is approved for use in allergic diseases of the airways (asthma), nasal cavity (chronic rhinosinutis with nasal polyps) and skin (spontaneous urticaria). 2. Mepolizumab and reslizumab bind to IL-5 released from Th2 and ILC2 cells, inhibiting its ability to interact with IL-5R on eosinophils. Benralizumab binds to the IL-5Rα subunit via its Fab region, similarly preventing IL-5 interaction. Benralizumab also binds to the FcγRIIIa subunit on NK cells via its Fc region, initiating ADCC through perforin and granzyme B secretion. Mepolizumab, reslizumab and benralizumab are approved for use in the airways (asthma) and mepolizumab is under approval review from the FDA for the treatment of chronic rhinosinutis with nasal polyps. 3. Dupilumab inhibits IL-4 and IL-13 released from Th2 and ILC2 cells from interacting with their shared IL-4Rα subunit. This in turn prevents IL-4-mediated stimulation of soluble IgE synthesis from B-cells and activation of basophils, reducing their associated immune mediator release. Inhibition of IL-13 reduces goblet cell hypertrophy and mucus production. Dupilumab is approved for use in the airways (asthma), nasal cavity (chronic rhinosinutis with nasal polyps) and skin (atopic dermatitis). Bθ, basophils; Eθ, eosinophils; Th2, T helper type 2 cell; IgE, immunoglobulin E; ILC2, type 2 innate lymphoid cell; IL-5R, IL-5 receptor; IL-4R, IL-4 receptor; IL-13R, IL-13 receptor; FcεRI, high affinity IgE receptor; FcγRIIIa, low low-affinity Fc receptor for immune-complexed IgG; NK, natural killer cells; ADCC, antibody-dependent cellular cytotoxicity.