IgE-activated mast cells in combination with pro-inflammatory factors induce Th2-promoting dendritic cells
IgE-activated mast cells in combination with pro-inflammatory factors induce Th2-promoting dendritic cells
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DOI：
10.1093/intimm/dxl113
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发表时间：
2006-12-01
影响因子：
4.4
通讯作者：
Uchiyama, Takashi
中科院分区：
文献类型：
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作者：
Kitawaki, Toshio;Kadowaki, Norimitsu;Uchiyama, Takashi
树突状细胞（DC）和肥大细胞（MC）共定位于抗原进入的外周组织，即皮肤和粘膜。由于这两种细胞类型的接近，MC 的激活可能会影响 DC 的功能。在这里，我们将人单核细胞来源的 DC 与通过 Fc epsilon RI 交联激活的脐带血来源的 MC 共培养，以阐明整个 MC 产品对 DC 的净效应。激活的 MC 诱导 DC 成熟，并有效抑制 DC 产生 IL-12p70。 DCs与活化的MCs单独共培养并没有显着影响DCs诱导的CD4(+)T细胞反应类型，而在促炎或T(h)1诱导因子存在的情况下DCs与活化的MCs共培养会引起T(h)2极化。尽管组胺参与激活 MC 诱导 DC 成熟和 T(h)2 极化，但需要多种 MC 衍生因子（包括以细胞接触依赖性方式起作用的因子）的组合作用，才能最佳诱导 T(h)2 促进 DC。此外，我们还证明，在特应性皮炎的皮损中，DC 簇与 MC 紧密相连。总的来说，这项研究表明，在促炎甚至易发生 T(h)1 的环境中，DC 和 IgE 激活的 MC 之间的相互作用有助于维持和增强过敏中的 T(h)2 反应，并且破坏 DC-MC 相互作用可能构成治疗持续过敏性疾病的有效策略。
Dendritic cells (DCs) and mast cells (MCs) co-localize in peripheral tissues of antigen entry, i.e. skin and mucosa. Due to the proximity of these two cell types, activation of MCs may affect DC functions. Here, we co-cultured human monocyte-derived DCs with cord blood-derived MCs activated by cross-linking of Fc epsilon RI to elucidate the net effect of the whole MC products on DCs. Activated MCs induced maturation of DCs, and potently suppressed IL-12p70 production by the DCs. Whereas co-culture of DCs with activated MCs alone did not significantly influence the type of CD4(+) T cell responses induced by the DCs, DCs co-cultured with activated MCs in the presence of pro-inflammatory or T(h)1-inducing factors caused T(h)2 polarization. Although histamine was involved in the induction of DC maturation and T(h)2 polarization by activated MCs, a combinatorial effect of various MC-derived factors, including those acting in a cell contact-dependent manner, was required for the optimal induction of T(h)2-promoting DCs. Furthermore, we demonstrated that clusters of DCs are located closely with MCs in lesions of atopic dermatitis. Collectively, this study suggests that the interaction between DCs and IgE-activated MCs in a pro-inflammatory or even T(h)1-prone environment is instrumental in maintaining and augmenting T(h)2 responses in allergy, and that disruption of the DC-MC interaction may constitute an effective strategy to treat ongoing allergic diseases.