Institute of Microbiology and Immunology, College of Medicine, National Cheng Kung University Hospital, Tainan, Taiwan.
Mucosal Immunol. 2011 Sep;4(5):519-27. doi: 10.1038/mi.2011.17. Epub 2011 Apr 6.
House dust mites (HDMs) induce allergic asthma in sensitized individuals, although how HDMs activate immature mucosal dendritic cells (DCs) to render the T helper cell type 2 (Th2)-mediated immune response is unclear. In this study, our results showed a significant calcium-dependent lectin binding of Dermatophagoides pteronyssinus (Der p) extracts to DC-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN), the C-type lectin receptors (CLRs) of DCs. Moreover, monocyte-derived DCs (MDDCs) of Der p-sensitized asthmatics (AS) exhibited decreased expression of DC-SIGN, increased endocytosis, and impaired differentiation of DC precursors. The Der p-induced downregulation of DC-SIGN expression in the differentiation of immature MDDCs may be because of the internalization of Der p-DC-SIGN complex. MDDCs of AS produced more interleukin (IL)-6 and less IL-12p70 cytokines when stimulated with lipopolysaccharide (LPS) or Der p than those of nonallergic controls (NC). In the co-culture experiments, MDDCs pretreated with Der p induced GATA-3 expression and IL-4 cytokine productions in naive CD4(+) T cells. These effects of Der p on the differentiation and function of MDDCs could be partially blocked by anti-DC-SIGN antibodies. In conclusion, our results suggest a critical step of allergen sensitization that involves CLRs in the innate immune response of DCs, which may provide a therapeutic or preventive potential for allergic asthma.
屋尘螨（HDM）可使致敏个体发生变应性哮喘，但 HDM 如何激活未成熟黏膜树突状细胞（DC）从而引发辅助性 T 细胞 2（Th2）介导的免疫反应尚不清楚。在本研究中，我们的结果表明，屋尘螨提取物与 DC 特异性细胞间黏附分子 3 捕获非整合素（DC-SIGN），即 DC 的 C 型凝集素受体（CLRs）之间存在显著的钙依赖性凝集素结合。此外，尘螨致敏哮喘（AS）患者来源的单核细胞衍生树突状细胞（MDDC）中 DC-SIGN 的表达降低，内吞作用增加，DC 前体分化受损。Der p 诱导未成熟 MDDC 分化过程中 DC-SIGN 表达下调可能是由于 Der p-DC-SIGN 复合物的内化。与非过敏对照（NC）相比，AS 患者来源的 MDDC 在用脂多糖（LPS）或 Der p 刺激时产生更多的白细胞介素（IL）-6 和更少的 IL-12p70 细胞因子。在共培养实验中，用 Der p 预处理的 MDDC 可诱导幼稚 CD4+T 细胞中 GATA-3 表达和 IL-4 细胞因子产生。抗 DC-SIGN 抗体可部分阻断 Der p 对 MDDC 分化和功能的影响。总之，我们的结果表明，这是过敏原致敏的一个关键步骤，涉及 DC 固有免疫反应中的 CLRs，这可能为变应性哮喘提供治疗或预防的潜在靶点。
