Soluble IgE receptors--elements of the IgE network

Abstract

Soluble isoforms of three human IgE Fc receptors, namely FcεRI, FcεRII, and galectin-3, can be found in serum. These soluble IgE receptors are a diverse family of proteins unified by the characteristic of interacting with IgE in the extracellular matrix. A truncated form of the alpha-chain of FcεRI, the high affinity IgE receptor, has recently been described as a soluble isoform (sFcεRI). Multiple soluble isoforms of CD23 (sCD23), the low affinity IgE receptor also known as FcεRII, are generated via different mechanisms of extracellular and intracellular proteolysis. The second low affinity IgE receptor, galectin-3, only exists as a secretory protein. We here discuss the physiological roles of these three soluble IgE receptors as elements of the human IgE network. Additionally, we review the potential and current use of sFcεRI, sCD23, and galectin-3 as biomarkers in human disease.

Figure 1

Human IgE Fc-receptors and their soluble isoforms. The high affinity IgE Fc receptor, Fc-epsilon-RI (FcεRI), has two transmembrane isoforms, FcεRIαβγ₂ and FcεRIαγ₂. The soluble isoform, sFcεRI, is a single chain receptor consisting of a truncated version of the IgE-binding FcεRIα subunit. Several different soluble isoforms of the transmembrane low affinity IgE Fc receptor, FcεRII or CD23, have been described. A detailed summary of soluble CD23 (sCD23) isoforms and their cleavage sites is provided in Table 2. Galectin-3 is a secretory IgE Fc receptor. After secretion, galectin-3 can attach to cell membranes via interacting with a large number of carbohydrate structures displayed by cell surface proteins. Additionally, an intracellular pool of galectin-3 can be found in the cytoplasm and the nucleus.

Figure 2

Possible interaction partners of soluble Fc-epsilon-RI (sFcεRI) in vivo. A) FcεRI exists as a membrane bound as well as a soluble isoform in human blood. In serum, sFcεRI is found as a true soluble form or as a sFcεRI-IgE complex when bound to its natural ligand. Potentially, sFcεRI-IgE complexes can interact with antigens and form immune complexes of higher order. Free sFcεRI can additionally interact with membrane IgE expressed on B cells. sFcεRI-IgE complexes cannot bind to trimeric or tetrameric FcεRI expressed on the cell surface of peripheral blood cells, because the binding site of IgE and the cellular receptor is blocked by sFcεRI in solution. B) In tissue, all interactions described for peripheral blood in (A) are theoretically possible. It remains to be defined whether the local concentration of sFcεRI in tissue is comparable to sFcεRI serum levels. Cells migrating from the periphery blood could also serve as vehicles to transport sFcεRI into tissue.