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

被引:97
作者
Novak, N
Tepel, C
Koch, S
Brix, K
Bieber, T
Kraft, S
机构
[1] Univ Bonn, Dept Dermatol, D-53105 Bonn, Germany
[2] Univ Bonn, Inst Cell Biol, D-53105 Bonn, Germany
[3] Univ Bonn, Bonner Forum Biomed, D-53105 Bonn, Germany
[4] Harvard Univ, Sch Med, Boston, MA USA
[5] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA
关键词
D O I
10.1172/JCI200315932
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
While mast cells and basophils constitutively express the high-affinity IgE receptor (FcepsilonRI), it is absent or weakly expressed on APCs from normal donors. FcFRI is strongly upregulated on APCs from atopic donors and involved in the pathophysiology of atopic diseases. Despite its clinical relevance, data about FcepsilonRI regulation on APCs are scarce. We show that in all donors intracellular a chain of the FcepsilonRI (FcepsilonRIalpha) accumulates during DC differentiation from monocytes. However, expression of gamma chains of the FcepsilonRI (FcERIgamma), mandatory for surface expression, is downregulated. It is low or negative in DCs from normal donors lacking surface FcepsilonRI (FCFRIneg DCs). In contrast, DCs from atopics express surface FcepsilonRI (FcFRI(pos) DCs) and show significant FceRIgamma expression, which can be coprecipitated with FCFRIalpha. In FcepsilonRI eg DCs lacking FcFRIgamma, immature and core glycosylated FcepsilonRIalpha accumulates in the endoplasmic reticulum. In FcepsilonRI(pos) DCs expressing FcepsilonRfgamma, an additional mature form of FcepsilonRIalpha exhibiting complex glycosylation colocalizes with FcepsilonRIgamma in the Golgi compartment. IgE binding sustains surface-expressed FcepsilonERI on DCs from atopic donors dependent on baseline protein synthesis and transport and enhances their IgE-dependent APC function. We propose that enhanced FcFRI on DCs from atopic donors is driven by enhanced expression of otherwise limiting amounts of FcepsilonRIgamma and is preserved by increased IgE levels.
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页码:1047 / 1056
页数:10
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