Evidence for a differential expression of the FcεRIγ chain in dendritic cells of atopic and nonatopic donors
Evidence for a differential expression of the FcεRIγ chain in dendritic cells of atopic and nonatopic donors
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DOI：
10.1172/jci200315932
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发表时间：
2003-04-01
影响因子：
15.9
通讯作者：
Kraft, S
中科院分区：
文献类型：
--
作者：
Novak, N;Tepel, C;Kraft, S
虽然肥大细胞和嗜碱性粒细胞组成型表达高亲和力IgE受体（FcepsilonRI），但它在正常供体的APC上不存在或弱表达。FcFRI在来自特应性供体的APC上强烈上调，并参与特应性疾病的病理生理学。尽管其临床相关性，但关于FcepsilonRI对APC的调节的数据很少。我们发现，在所有捐助者的细胞内的FcepsilonRI（FcepsilonRIalpha）的链积累在DC分化单核细胞。然而，表面表达所必需的Fc ε RI γ链（FcERIgamma）的表达下调。在来自缺乏表面FcepsilonRI的正常供体的DC（FCFRIneg DC）中其是低的或阴性的。相比之下，来自特应性的DC表达表面Fc ε RI（FcFRI（pos）DC）并显示显著的FceRI γ表达，其可以与FCFRI α共沉淀。在缺乏FcFR1 γ的Fc ε RI eg DC中，未成熟的和核心糖基化的Fc ε RI α在内质网中积累。在表达Fc ε RI γ的Fc ε RI（pos）DC中，表现出复杂糖基化的另外成熟形式的Fc ε RI α与Fc ε RI γ共定位在高尔基体区室中。IgE结合维持来自特应性供体的DC上依赖于基线蛋白质合成和转运的表面表达的Fc ε ERI，并增强其IgE依赖性APC功能。我们提出，增强的FcFRI对DC从特应性供体是由增强的表达，否则限制量的Fc ε RI γ和保持IgE水平的增加。
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.