The Affiliated People's Hospital, and School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang, Jiangsu Province, PR China.
Cell Immunol. 2011;270(2):183-7. doi: 10.1016/j.cellimm.2011.05.003. Epub 2011 May 10.
β-Glucans have been shown to enhance immune responses for centuries, which contributes to their anti-tumor property. However, their mechanisms of action are still elusive. Dectin-1, the C-type lectin receptor for β-glucan, is expressed abundantly on dendritic cells (DCs). Activation of DCs via Dectin-1 can lead to the maturation of DC, inducing both innate and adaptive immune responses against tumor development and microbial infection. In this study, we found that particulate yeast-derived β-glucans could induce the maturation of murine dendritic cell line D2SC/1 cells and increase the expression of mGITRL on D2SC/1 cells via Dectin-1/Syk pathway in a dose dependent manner. Furthermore, we demonstrated that the increased mGITRL on D2SC/1 cells could impair the suppressive activity of CD4(+)CD25(+) regulatory T cells (Tregs) and enhance the proliferation of CD4(+)CD25(-) effector T cells (Teffs). These findings suggest that particulate β-glucan can be used as immunomodulator to stimulate potent T cell-mediated adaptive immunity while down-regulate immune suppressive activity, leading to a more efficient defense mechanism against tumor development or infectious diseases.
β-葡聚糖几个世纪以来被证明可以增强免疫反应，这有助于其抗肿瘤特性。然而，其作用机制仍难以捉摸。Dectin-1 是 β-葡聚糖的 C 型凝集素受体，在树突状细胞（DC）上大量表达。通过 Dectin-1 激活 DC 可导致 DC 的成熟，诱导针对肿瘤发展和微生物感染的先天和适应性免疫反应。在这项研究中，我们发现颗粒状酵母来源的β-葡聚糖可以通过 Dectin-1/Syk 途径诱导小鼠树突状细胞系 D2SC/1 细胞的成熟，并呈剂量依赖性增加 D2SC/1 细胞上的 mGITRL 表达。此外，我们证明 D2SC/1 细胞上增加的 mGITRL 可以削弱 CD4+CD25+调节性 T 细胞（Tregs）的抑制活性，并增强 CD4+CD25-效应 T 细胞（Teffs）的增殖。这些发现表明，颗粒状β-葡聚糖可用作免疫调节剂，刺激有效的 T 细胞介导的适应性免疫，同时下调免疫抑制活性，从而形成针对肿瘤发展或传染病的更有效的防御机制。
