Rethinking the role of immunoglobulin E and its high-affinity receptor: new insights into allergy and beyond

Immunoglobulin E (IgE) and its high-affinity receptor (FcεRI) are well-known participants in the allergic response. The interaction of allergens with FcεRI-bound IgE antibodies is an essential step in mast cell/basophil activation and the subsequent release of allergic mediators. It is known that the affinity of the interaction between an IgE antibody and an allergen may differ, raising the question of whether FcεRI can decipher these differences. If so, do the cellular and physiological outcomes vary? Are the molecular mechanisms initiated by FcεRI similarly under low- or high-affinity interactions? Could the resulting inflammatory response differ? Recent discoveries summarized herein are beginning to shed new light on these important questions. What we have learned from them is that IgE and FcεRI form a complex regulatory network influencing the inflammatory response in allergy and beyond.