Abstract
The recent emergence of anti-immunoglobulin E (IgE) drugs and their candidates for humans has endorsed the significance of IgE-dependent pathways in allergic disorders. IgE is distributed locally in the tissues or systemically to confer a sensory mechanism in a domain of adaptive immunity to the otherwise innate type of effector cells, namely, mast cells and basophils. Bound on the high-affinity IgE receptor FcεRI, IgE enables fast memory responses against revisiting threats of venoms, parasites, and bacteria. However, the dysregulation of IgE-dependent reactions leads to potentially life-threatening allergic diseases, such as asthma and anaphylaxis. Therefore, reactivity of the IgE sensor is fine-tuned by various IgE-associating molecules. In this review, we discuss the mechanistic basis for how IgE-dependent mast cell activation is regulated by the IgE-associating molecules, including the newly developed therapeutic candidates.
Highlights
The recent emergence of anti-immunoglobulin E (IgE) drugs and their candidates for humans has endorsed the significance of IgE-dependent pathways in allergic disorders
In addition to the well-established knowledge obtained from animal models, the central role of IgE in allergic diseases in humans has been endorsed by the emergence of anti-IgE therapy by omalizumab, effective against various allergic diseases, including asthma, chronic spontaneous urticaria, nasal polyps, and allergic rhinitis
The efforts to elucidate the true nature of IgE have revealed that this single molecule, has a diversity; the conformation is flexible, the glycosylation may change in health and diseases, and the reactivity to antigens and IgE-interacting molecules such as histamine-releasing factor may vary
Summary
The high-affinity receptor FcεRI is a heterotetramer, comprising an IgE-binding α chain, a signal-amplifying β chain, and two signalface, and Lyn initiates the activation cascade by phosphorylating ITAMs, leading to a wide range of events, including degranulation, de novo lipid mediator synthesis, cytokine and chemokine production, as well as chemotaxis and survival of mast cells. Upon the engagementSH2 of multimain-containing protein tyrosine phosphatase (SHP-1), through the phosphorylation of valent antigens on FcεRI-bound IgEs, these receptors aggregate on the mast cell surface, β and chainLyn. ITAM, thereby providing safety mechanisms [17]. Anti-IgE monoclonal antibodies effectively crosslink IgE and activate mast cells, suggesting that the valency of two is sufficient for the cognate antigen to form clusters. Monomeric HRF-2CA may be a good candidate for the drug targeting HRF
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
