Immunologically mediated signaling in basophils and mast cells: finding therapeutic targets for allergic diseases in the human FceR1 signaling pathway

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Christopher Kepley, Associate Professor (Creator)
The University of North Carolina at Greensboro (UNCG )
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Abstract: The high affinity IgE receptor, FceRI, plays key roles in an array of acute and chronic human allergic reactions including asthma, allergic rhinitis, atopic dermatitis, urticaria and anaphylaxis. In humans and rodents, this receptor is found at high levels on basophils and mast cells where its activation by IgE and multivalent antigen produces mediators and cytokines responsible for FceRI-dependent acute inflammation. Mast cells can additionally contribute to sustained inflammatory responses by internalizing antigen bound to IgE-FceRI complexes for processing to peptides and presentation to T cells. In humans, the FceRI is also expressed, at lower density, on monocytes, macrophages and dendritic cells (DC) where its likely functions again include both signaling to mediator and cytokine production and antigen presentation. Our laboratories have focused on defining the earliest steps in the FceRI signaling cascade in basophils and mast cells and on developing new routes to control allergic inflammation based on inhibiting these events. Here, we describe novel strategies to limit antigen-stimulated FceRI signaling by: (1) sequestering the FceRI-associated protein-tyrosine kinase, Lyn, that initiates FceRI signaling; (2) eliminating; or (3) inactivating the protein-tyrosine kinase, Syk, that propagates FceRI signaling; and (4) establishing inhibitory crosstalk between FceRI and a co-expressed receptor, FcgRII, that again limits FceRI-mediated Syk activation. These strategies may form the basis for new therapies for allergic inflammation.

Additional Information

Immunopharmacology 2000; 48(3):269-81.
Language: English
Date: 2000
Basophil, Mast cell, IgE, FceRI, IgG, FcgRII, Allergy, Inflammation, Asthma, Tyrosine kinase, Lyn, Syk, Antigen-presenting cells, ITAM, ITIM, Anti-IgE, Secretion, Degranulation, Cytokine production, Piceatannol, Immunotherapy

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