IL-4 induces the intracellular expression of the α chain of the high-affinity receptor for IgE in in vitro-generated dendritic cells
IL-4 induces the intracellular expression of the α chain of the high-affinity receptor for IgE in in vitro-generated dendritic cells
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DOI：
10.1016/s0091-6749(00)90190-8
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发表时间：
2000-01-01
影响因子：
14.2
通讯作者：
Bieber, T
中科院分区：
文献类型：
--
作者：
Geiger, E;Magerstaedt, R;Bieber, T
背景：最近的研究结果表明，IgE高亲和受体（Fc epsilon RI）在人CD1a（+）朗格汉斯细胞（LC）和皮肤中相关树突状细胞（DC）的表面表达，尽管其α链（Fc epsilon RI α）在细胞内持续表达，但在特应性皮炎中高度上调。此外，该表面表达与IgE血清水平相关，强烈提示在LC/DC和IgE合成上调节Fc epsilon RI显示的共同信号尚未确定。目的：研究不同细胞因子对体外生成CD1a(+) LC/DC细胞Fc epsilon RI表达的影响；方法：采用高梯度磁细胞分选分离脐带血CD34（+）前体细胞，GM-CSF培养；流式细胞术进行tnf - α， IL-4或ifn - γ，表面和细胞质染色。结果：IL-4强烈增强CD1a(+) LC/DC的生成，并上调皮肤归巢结构E-cadherin和皮肤淋巴细胞抗原的表达，而ifn - γ则通过抑制CD1a（+）细胞的产生抑制E-cadherin的表达，并成为IL-4的强拮抗剂。最重要的是，IL-4诱导CD1a(+) LC/DC细胞质中Fc epsilon RI α的表达，而非其表面表达。这种上调被ifn - γ拮抗。结论：IL-4不仅是调控IgE的关键细胞因子，还可诱导其受体结合链的表达，并上调LC/DC上皮肤归巢分子的表达。这些结构在LC/DC生成过程中的表达反映了LC在体内所遇到的情况。
Background: Recent findings have shown that the surface expression of the high-affinity receptor for IgE (Fc epsilon RI) on human CD1a(+) Langerhans cells (LC) and related dendritic cells (DC) in the skin, despite a constant intracellular expression of its alpha chain (Fc epsilon RI alpha), is highly up-regulated in atopic dermatitis. Moreover, this surface expression correlates with the IgE serum level, strongly suggesting yet-to-be-defined common signals in the regulation of Fc epsilon RI display on LC/DC and IgE synthesis.Objectives: In this study me examined the influence of different cytokines on the expression of Fc epsilon RI on in vitro-generated CD1a(+) LC/DC;Methods: CD34(+) precursor cells were isolated from cord blood with use of high-gradient magnetic cell sorting, cultured with GM-CSF; TNF-alpha, IL-4, or IFN-gamma, and surface and cytoplasmic staining for flow cytometry were performed.Results: IL-4 strongly enhanced the generation of CD1a(+) LC/DC and also up-regulated the expression of the skin-homing structures E-cadherin and cutaneous lymphocyte antigen, In contrast, IFN-gamma was found to suppress the E-cadherin expression and to be a strong antagonist of IL-4 by inhibiting the production of CD1a(+) cells. Most important, IL-4 induced the cytoplasmic expression of Fc epsilon RI alpha in CD1a(+) LC/DC but not its surface expression. This up-regulation was antagonized by IFN-gamma.Conclusion: IL-4 is not only a key cytokine in the regulation of IgE hut also induces the expression of its receptor binding chain as well as up-regulation of skin homing molecules on LC/DC. Expression of these structures during generation of LC/DC reflects the in vivo situation encountered in LC.