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 5

FCER1A-Tg mice express and localize hFcεRI in a similar manner to humans.

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FCER1A-Tg mice express and localize hFcεRI in a similar manner to human...
(A) Surface expression of hFcεRI in FCER1A-Tg mouse blood leukocytes. Blood from adult hFcεRIα(+) transgenic (Tg+, black) and hFcεRIα(–) (Tg–, gray shaded) littermates was collected and stained with an anti-hFcεRIα antibody and cell type–specific antibodies after red blood cell lysis. Gating strategies are shown in Supplemental Figure 6A. (B) Intracellular localization of hFcεRI in Tg+ mouse blood basophils and monocytes. Sorted blood basophils and monocytes were stained for confocal microscopy as described for Figure 2. Images are representative of results from 3 independent experiments. Note that the calnexin signal has been switched from blue to cyan for ease of visualization in single-stain format, while it has not been altered for merged images. (C) Intracellular localization of hFcεRI in Tg+ mouse CD11b+ BMDCs. BMDCs were cultured using Flt3L, sorted for CD11b+ cDCs as described for Supplemental Figure 6B, and stained as in B. Images are representative results from 3 independent experiments. For all confocal images, magnification was ×60, scale bars are 2.5 μm, and negligible staining by isotype control antibodies was confirmed (Supplemental Figure 7).