Evidence for a differential expression of the FcepsilonRIgamma chain in dendritic cells of atopic and nonatopic donors.
While mast cells and basophils constitutively express the high-affinity IgE receptor (Fc epsilon RI), it is absent or weakly expressed on APCs from normal donors. Fc epsilon RI is strongly upregulated on APCs from atopic donors and involved in the pathophysiology of atopic diseases. Despite its clinical relevance, data about Fc epsilon RI regulation on APCs are scarce. We show that in all donors intracellular alpha chain of the Fc epsilon RI (Fc epsilon RI alpha) accumulates during DC differentiation from monocytes. However, expression of gamma chains of the Fc epsilon RI (Fc epsilon RI gamma), mandatory for surface expression, is downregulated. It is low or negative in DCs from normal donors lacking surface Fc epsilon RI (Fc epsilon RI(neg) DCs). In contrast, DCs from atopics express surface Fc epsilon RI (Fc epsilon RI(pos) DCs) and show significant Fc epsilon RI gamma expression, which can be coprecipitated with Fc epsilon RI alpha. In Fc epsilon RI(neg) DCs lacking Fc epsilon RI gamma, immature and core glycosylated Fc epsilon RI alpha accumulates in the endoplasmic reticulum. In Fc epsilon RI(pos) DCs expressing Fc epsilon RI gamma, an additional mature form of Fc epsilon RI alpha exhibiting complex glycosylation colocalizes with Fc epsilon RI gamma in the Golgi compartment. IgE binding sustains surface-expressed Fc epsilon RI on DCs from atopic donors dependent on baseline protein synthesis and transport and enhances their IgE-dependent APC function. We propose that enhanced Fc epsilon RI on DCs from atopic donors is driven by enhanced expression of otherwise limiting amounts of Fc epsilon RI gamma and is preserved by increased IgE levels.
Novak
Natalija
N
Department of Dermatology, Friedrich-Wilhelms University, Bonn, Germany.
Tepel
Carmen
C
Koch
Susanne
S
Brix
Klaudia
K
Bieber
Thomas
T
Kraft
Stefan
S
D000941:Antigens / Q000378:metabolism; D001249:Asthma / Q000276:immunology / Q000378:metabolism; D015153:Blotting, Western; D002454:Cell Differentiation; D003231:Conjunctivitis / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism*; D003876:Dermatitis, Atopic / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation; D004721:Endoplasmic Reticulum / Q000276:immunology / Q000378:metabolism; D006026:Glycoside Hydrolases / Q000378:metabolism; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D011233:Precipitin Tests; D012333:RNA, Messenger / Q000378:metabolism; D017455:Receptors, IgE / Q000096:biosynthesis* / Q000235:genetics*; D013997:Time Factors; D015854:Up-Regulation
D000941:Antigens; D012333:RNA, Messenger; D017455:Receptors, IgE; D007073:Immunoglobulin E; D006026:Glycoside Hydrolases