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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.