IgE signaling suppresses FcepsilonRIbeta expression.

Activation of the high-affinity receptor for IgE, FcepsilonRI, is known to elicit its rapid down-regulation through internalization and degradation. In keeping with this, expression of all three FcepsilonRI subunits is decreased at the protein level after cross-linkage of IgE with antigen. However, we find that the FcepsilonRI beta-subunit is also selectively suppressed at the mRNA level, through a pathway primarily involving Fyn, Syk, PI3K, and NF-kappaB. IgG or calcium ionophore, stimuli known to mimic portions of the IgE signaling cascade, similarly suppressed beta-subunit expression. LPS, a NF-kappaB-activating TLR ligand, did not alter beta-subunit expression. As IgE increases FcepsilonRI expression, we examined the coordinated regulation of FcepsilonRI subunits during culture with IgE, followed by cross-linkage with antigen. IgE increased the expression of all three FcepsilonRI 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. FcepsilonRIbeta is a key regulator of IgER expression and function, a gene in which polymorphisms correlate with allergic disease prevalence. The ability of IgE and FcepsilonRI 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.