Fc receptors as determinants of allergic reactions

Activation of the high-affinity receptor for IgE (FcepsilonRI) on allergic effector cells induces a multitude of positive signals via immunoreceptor tyrosine-based activation motifs, which leads to the rapid manifestation of allergic inflammatory reactions. As a counterbalance, the coaggregation of the IgG receptor FcgammaRIIB mediates inhibitory signals via immunoreceptor tyrosine-based inhibition motifs. Advances in the positive and negative regulation of Fc receptor expression and signaling have shed light on the role of Fc receptors in our immune system, indicating them to be bifunctional, inhibitory and activating structures. Based on these findings, exciting new therapeutic strategies have been developed, such as the use of chimeric fusion proteins, which concomitantly activate FcepsilonRI and FcgammaRIIB. These new approaches successfully take advantage of the bivalent character of Fc receptors and pave the way for innovative strategies to modulate allergic immune reactions.