Serum IgE clearance is facilitated by human FcεRI internalization

The high-affinity IgE receptor FcERI is constitutively expressed in mast cells and basophils and is required for transmitting stimulatory signals upon engagement of IgE-bound allergens. FcERI is also constitutively expressed in d.end.ritic cells (DCs) and monocytes in humans; however, the specific functions of the FcERI expressed by these cells are not completely understood. Here, we found that FcERI expressed by human blood DC antigen 1-positive (BDCAl+) DCs and monocytes, but not basophils, traffics to endnlysosomal compartments under steady-state conditions. Furthermore, IgE bound to FcERI on BDCA.1 DCs was rapidly endocytosed, transported to the lysosomes, and degraded in vitro. IgE injected into mice expressing human FccRIa (FCER1A-Tg mice) was endocytosed by conventional DCs and monocytes, and endocytosis was associated with rapid clearance of circulating IgE from these mice. Importantly, this rapid IgE clearance was dependent on monocytes or DCs but not basophils. These findings strongly suggest that constitutive internalization of human FcERI by DCs and monocytes distinctively contributes to serum IgE clearance.