In recent years, studies have begun to reveal the structure, signal transduction, and function of IgE receptors of different cell types in rodent and human systems. IgE receptors are important parts of immune pathways in allergic and inflammatory diseases. At present, three human soluble IgE receptors have been described: soluble FcεRI (sFcεRI), soluble CD23 (sCD23), and galectin-3.
FcεRI
sFcεRI is a single-chain receptor isoform of FcεRI, the high-affinity IgE receptor. This receptor isoform is well known for its function as a key regulator of allergic responses. When IgE-specific antigen crosslinks the receptor, the release of preformed inflammatory mediators and cytokines is triggered. Thus, IgE-FcεRI mediated activation of mast cells and basophils is considered a hallmark of immediate allergic reactions. Immunoprecipitation studies from human serum show that sFcεRI consists of a smaller FcεRI alpha-chain with a molecular weight of ~40 kDa compared to the ~60 kDa full-length protein.
FcεRII
CD23 (sCD23), the low-affinity IgE receptor also known as FcεRII, is generated via different mechanisms of extracellular and intracellular proteolysis. sCD23 molecules result from proteolytic cleavage of the 45 kDa transmembrane form of the low-affinity receptor for IgE, FcεRII. The role of FcεRII in allergic diseases and inflammatory processes has been studied extensively, and its implication in IgE synthesis and IgE-mediated immune and inflammatory functions has been reviewed recently. Investigations in allergic rats revealed that enhanced intestinal transepithelial antigen transport is mediated by IgE and FcεRII.
Galectin-3
Galectin-3 is a secreted protein, about 30 kDa, belonging to the β-galactoside-binding animal lectin family. Because of its ability to interact with IgE as well as FcεRI, the protein was previously known as an ε-binding protein. Unlike FcεRI and CD23, galectin-3 does not exist as a transmembrane protein. The structure of galectin-3 includes a carbohydrate recognition domain (CRD) that is linked to the non-lectin domain of proline and glycine tandem repeats.
Fig.1 Human IgE Fc-receptors and their soluble isoforms. (Platzer, 2011)
The soluble IgE receptors CD23 and galectin-3 are upregulated in a variety of diseases and have made their way into clinical practice as diagnostic biomarkers. Soluble IgE receptors in human serum are a diverse group of proteins with the unifying characteristic of interacting with IgE. The regulation of IgE is associated intimately with specific receptors and other binding factors. CD23 seems to be the most important receptor affecting IgE production, while additional receptors at mucosal surfaces, so far poorly described, may be responsible for the elimination of most IgE. Although the advent of animal models of allergic disease and sophisticated molecular and immunologic reagents have provided a wealth of new information on induction and regulation of the IgE response, we are far from having a complete understanding of this important topic. Already the data indicate several new therapeutic avenues for the amelioration of allergic disease, including strategies that target IL-4, IL-13, and their receptors.
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Reference
- Platzer, B.; et al. Soluble IgE receptors-elements of the IgE network. Immunol Lett. 2011 Dec 30;141(1):36-44.
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