Evidence for a differential expression of the FcεRIγ chain in dendritic cells of atopic and nonatopic donors
Natalija Novak, … , Thomas Bieber, Stefan Kraft
Natalija Novak, … , Thomas Bieber, Stefan Kraft
Published April 1, 2003
Citation Information: J Clin Invest. 2003;111(7):1047-1056. https://doi.org/10.1172/JCI15932.
View: Text | PDF
Article Genetics

Evidence for a differential expression of the FcεRIγ chain in dendritic cells of atopic and nonatopic donors

Abstract

While mast cells and basophils constitutively express the high-affinity IgE receptor (FcεRI), it is absent or weakly expressed on APCs from normal donors. FcεRI is strongly upregulated on APCs from atopic donors and involved in the pathophysiology of atopic diseases. Despite its clinical relevance, data about FcεRI regulation on APCs are scarce. We show that in all donors intracellular α chain of the FcεRI (FcεRIα) accumulates during DC differentiation from monocytes. However, expression of γ chains of the FcεRI (FcεRIγ), mandatory for surface expression, is downregulated. It is low or negative in DCs from normal donors lacking surface FcεRI (FcεRIneg DCs). In contrast, DCs from atopics express surface FcεRI (FcεRIpos DCs) and show significant FcεRIγ expression, which can be coprecipitated with FcεRIα. In FcεRIneg DCs lacking FcεRIγ, immature and core glycosylated FcεRIα accumulates in the endoplasmic reticulum. In FcεRIpos DCs expressing FcεRIγ, an additional mature form of FcεRIα exhibiting complex glycosylation colocalizes with FcεRIγ in the Golgi compartment. IgE binding sustains surface-expressed FcεRI on DCs from atopic donors dependent on baseline protein synthesis and transport and enhances their IgE-dependent APC function. We propose that enhanced FcεRI on DCs from atopic donors is driven by enhanced expression of otherwise limiting amounts of FcεRIγ and is preserved by increased IgE levels.

Authors

Natalija Novak, Carmen Tepel, Susanne Koch, Klaudia Brix, Thomas Bieber, Stefan Kraft

×

Figure 6

Options: View larger image (or click on image) Download as PowerPoint
Addition of IgE leads to sustained FcεRI surface expression in DCs from ...
Addition of IgE leads to sustained FcεRI surface expression in DCs from atopic donors in a BFA- and CHX-sensitive process without affecting de novo synthesis of FcεRIα and FcεRIγ chains. (a) IgE was added from day 0 of DC culture (atopic donors) with GM-CSF and IL-4. Immunolabeling and flow-cytometric analysis of FcεRI surface expression was performed as described for Figure 1. Percentage of positive cells shown under a are the result of six independent experiments. (b) MoDCs (day 4) were incubated for 24 and 48 h with or without the addition of 1 μg/ml human myeloma IgE. After RNA isolation from highly purified MoDCs and reverse transcription, FcεRIα and FcεRIγ expression was analyzed by semiquantitative PCR using β-actin as a control. Shown is a representative experiment from an atopic donor of five total experiments. In parallel, FcεRIγ protein levels of one representative experiment of MoDC on day 6 of culture incubated with (+ IgE) and without IgE (– IgE) until day 4 of culture are shown (c). (d and e) MoDCs were generated with GM-CSF and IL-4 until day 4 of culture. Then IgE, CHX, and BFA (all 1 μg/ml) were added as indicated. Flow-cytometric analyses of FcεRI expression were done on days indicated. Mean FcεRI expression ± SEM (n = 7) is shown as percentage of FcεRI expression of monocytes at day 0.