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Serum IgE clearance is facilitated by human FcεRI internalization
Alexandra M. Greer, Nan Wu, Amy L. Putnam, Prescott G. Woodruff, Paul Wolters, Jean-Pierre Kinet, Jeoung-Sook Shin
Alexandra M. Greer, Nan Wu, Amy L. Putnam, Prescott G. Woodruff, Paul Wolters, Jean-Pierre Kinet, Jeoung-Sook Shin
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Research Article Immunology

Serum IgE clearance is facilitated by human FcεRI internalization

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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 6

Human IgE injected into FCER1A-Tg mice is internalized by cDCs and monocytes in the steady state.

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Human IgE injected into FCER1A-Tg mice is internalized by cDCs and monoc...
(A) Surface IgE levels on blood basophils and monocytes following human IgE injection. Before and at 1, 4, 8, and 24 hours after hIgE injection, Tg+ and Tg– mice were bled for flow cytometric analysis of surface IgE levels in basophils and monocytes. Data for Tg+ mice are shown in solid lines and for Tg– mice in dotted lines. Data for 3 mice from one representative experiment of 3 are presented with mean ± SEM. (B–D) Surface IgE levels on blood cDCs (B), lung DCs and monocytes (C), and peritoneal mast cells (D) of Tg+ mice following human IgE injection. At each time point following hIgE injection, mice were sacrificed and whole blood, lungs, or peritoneal lavage collected and analyzed by flow cytometry. Data for 9 mice (B), 8 mice (C), or 14 mice (D) from one representative experiment of 2 are presented with mean ± SEM. (E and F) Intracellular localization of human IgE in basophils and monocytes of FCER1A-Tg mice injected with hIgE. At 6 hours after injection, basophils and monocytes were isolated and examined for intracellular human IgE by confocal microscopy as described for Figure 3A. Original magnification, ×60; scale bars: 2.5 μm. (F) Intracellular IgE levels were quantified as in Figure 4B. Thirty images of Tg+ monocytes and basophils were analyzed. Resulting values are presented with mean ± SEM. *P < 0.05.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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