IgE signaling suppresses FcεRIβ expression

Activation of the high-affinity receptor for IgE, Fc epsilon RI, is known to elicit its rapid down-regulation through internalization and degradation. In keeping with this, expression of all three Fc epsilon RI subunits is decreased at the protein level after cross-linkage of IgE with antigen. However, we find that the Fc epsilon RI beta-subunit is also selectively suppressed at the mRNA level, through a pathway primarily involving Fyn, Syk, PI3K, and NF-kappa B. IgG or calcium ionophore, stimuli known to mimic portions of the IgE signaling cascade, similarly suppressed beta-subunit expression. LPS, a NF-kappa B-activating TLR ligand, did not alter beta-subunit expression. As IgE increases Fc epsilon RI expression, we examined the coordinated regulation of Fc epsilon RI subunits during culture with IgE, followed by cross-linkage with antigen. IgE increased the expression of all three Fc epsilon RI subunits and strikingly induced expression of the antagonistic beta(T). The ratio of beta:beta(T) protein expression decreased significantly during culture with IgE and was reset to starting levels by antigen cross-linkage. These changes in protein levels were matched by similar fluctuations in beta and beta(T) mRNAs. Fc epsilon RI beta is a key regulator of IgER expression and function, a gene in which polymorphisms correlate with allergic disease prevalence. The ability of IgE and Fc epsilon RI signaling to coordinate expression of the beta and beta(T) subunits may comprise a homeostatic feedback loop-one that could promote chronic inflammation and allergic disease if dysregulated. J. Leukoc. Biol. 86: 1351-1358; 2009.