Serum IgE clearance is facilitated by human FcεRI internalization
Alexandra M. Greer, … , Jean-Pierre Kinet, Jeoung-Sook Shin
Alexandra M. Greer, … , Jean-Pierre Kinet, Jeoung-Sook Shin
Published February 24, 2014
Citation Information: J Clin Invest. 2014;124(3):1187-1198. https://doi.org/10.1172/JCI68964.
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Research Article Immunology

Serum IgE clearance is facilitated by human FcεRI internalization

Abstract

The high-affinity IgE receptor FcεRI is constitutively expressed in mast cells and basophils and is required for transmitting stimulatory signals upon engagement of IgE-bound allergens. FcεRI is also constitutively expressed in dendritic cells (DCs) and monocytes in humans; however, the specific functions of the FcεRI expressed by these cells are not completely understood. Here, we found that FcεRI expressed by human blood DC antigen 1–positive (BDCA1+) DCs and monocytes, but not basophils, traffics to endolysosomal compartments under steady-state conditions. Furthermore, IgE bound to FcεRI on BDCA1+ DCs was rapidly endocytosed, transported to the lysosomes, and degraded in vitro. IgE injected into mice expressing human FcεRIα (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 FcεRI by DCs and monocytes distinctively contributes to serum IgE clearance.

Authors

Alexandra M. Greer, Nan Wu, Amy L. Putnam, Prescott G. Woodruff, Paul Wolters, Jean-Pierre Kinet, Jeoung-Sook Shin

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Figure 1

DCs regulate FcεRI surface expression more tightly than basophils.

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DCs regulate FcεRI surface expression more tightly than basophils. (A) G...
(A) Gating strategy of human basophils and DCs, and histograms of surface FcεRI expression and surface IgE bound to the cells. Anti-hFcεRIα antibody (CRA-1) and anti-hIgE staining are shown in black, and isotype control antibody staining is shown in grey. (B) Surface FcεRI levels of human blood basophils and DCs in healthy donors. PBMCs were analyzed for FcεRI expression by flow cytometry, and serum was analyzed for IgE concentration by ELISA. Isotype control stain MFI was subtracted from anti-hFcεRIα antibody stain MFI. Data for each donor were plotted according to serum IgE level. Lines of best fit were calculated and drawn; slope and r2 values are shown. (C) Surface IgE levels for the same donors as in B with similarly calculated lines of fit. (D) IgE occupancy rate of FcεRI in DCs as compared with basophils. The MFI of IgE was divided by the MFI of FcεRI for DCs and basophils after subtracting appropriate isotype control MFI values to generate an occupancy index. DC occupancy index was divided by basophil occupancy index to generate an occupancy rate of DCs compared with basophils.