Agricultural Biotechnology Research Center, Academia Sinica, Taiwan, ROC.
Cytokine. 2011 Jul;55(1):79-89. doi: 10.1016/j.cyto.2011.03.017. Epub 2011 Apr 12.
In this study, we compared the effects of zymosan and LPS on human monocyte-derived dendritic cells. The specific effects of zymosan on the expression of several key cytokines, including granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukins (IL-1α, IL-1β and IL-12 p70) were quite distinct from the effects of LPS. Unlike activation with LPS, DCs activated by zymosan expressed little or no IL-12 p70 due to lack of expression of the p35 subunit. However, treatment with zymosan resulted in a substantial increase in Th1 and Th17 cell-polarizing capacity of DCs. Furthermore, the GM-CSF secreted by zymosan-activated DCs enhanced IL-23 production, resulting in activation of a Th17 response. GM-CSF and IL-27, rather than IL-12 p70, were both major direct contributors to the activation of a Th1 response. This signaling mechanism is distinct and yet complementary to LPS-mediated T-cell activation. We suggest that this novel zymosan-induced GM-CSF-mediated signaling network may play a key role in regulating specific immune cell type activities.
在这项研究中，我们比较了酵母聚糖和 LPS 对人单核细胞来源的树突状细胞的影响。酵母聚糖对几种关键细胞因子表达的特定影响，包括粒细胞-巨噬细胞集落刺激因子（GM-CSF）和白细胞介素（IL-1α、IL-1β 和 IL-12 p70），与 LPS 的作用明显不同。与 LPS 激活不同，由于缺乏 p35 亚基的表达，酵母聚糖激活的 DCs 表达很少或不表达 IL-12 p70。然而，用酵母聚糖处理会导致 DCs 的 Th1 和 Th17 细胞极化能力显著增加。此外，酵母聚糖激活的 DCs 分泌的 GM-CSF 增强了 IL-23 的产生，导致 Th17 反应的激活。GM-CSF 和 IL-27，而不是 IL-12 p70，都是激活 Th1 反应的主要直接贡献者。这种信号机制与 LPS 介导的 T 细胞激活既独特又互补。我们认为，这种新型的酵母聚糖诱导的 GM-CSF 介导的信号网络可能在调节特定免疫细胞类型的活性中发挥关键作用。
