Sun Shuyu, Zheng Kang, Zhao Hongyan, Lu Cheng, Liu Biao, Yu Changyuan, Zhang Ge, Bian Zhaoxiang, Lu Aiping, He Xiaojuan
Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.
School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 611756, China.
Molecules. 2014 Sep 23;19(9):15224-36. doi: 10.3390/molecules190915224.
Astragalus polysaccharides (APS) possess multiple immunomodulatory activities. Due to its high molecular weight, orally administration of APS is not easily absorbed into the blood stream, and how APS exerts its capacity in vivo is still not well elucidated. We assume that enteric mucosal immune response might trigger the immune regulation of APS, and our previous studies demonstrated that APS had regulatory activity on intraepithelial lymphocytes (IELs). Therefore, this study aimed to investigate the functions of APS on intestinal intraepithelial γδT cells, a major subset in IELs and an essential component of maintaining homeostasis and immune regulation in enteric mucosa. Results showed that APS could promote proliferation and function of intestinal intraepithelial γδT cells in vitro, the IFN-γ, FasL and GrB mRNA levels in γδT cells were all significantly increased. Moreover, APS also improved the activity of intestinal intraepithelial γδT cells in vivo, as cytokines production and cytotoxicity of γδT cells were all remarkably improved in tumor-bearing mice treated with APS. In addition, the levels of TNF-α and IFN-γ were significantly increased, whereas the levels of IL-10 and TGF-β were significantly decreased in tumor-bearing mice treated with APS. In conclusion, this study demonstrated that APS could improve proliferation and function of intestinal intraepithelial γδT cells, which might an important pathway for immunomodulation of APS in cancer therapy.
黄芪多糖（APS）具有多种免疫调节活性。由于其分子量较大，口服 APS 不易被吸收进入血液循环，且 APS 在体内发挥作用的机制仍未完全阐明。我们推测肠道黏膜免疫反应可能触发 APS 的免疫调节作用，并且我们之前的研究表明 APS 对上皮内淋巴细胞（IELs）具有调节活性。因此，本研究旨在探讨 APS 对肠道上皮内γδT 细胞的作用，γδT 细胞是 IELs 的主要亚群，也是维持肠道黏膜稳态和免疫调节的重要组成部分。结果表明，APS 在体外可促进肠道上皮内γδT 细胞的增殖和功能，γδT 细胞中 IFN-γ、FasL 和 GrB 的 mRNA 水平均显著升高。此外，APS 在体内也增强了肠道上皮内γδT 细胞的活性，在用 APS 处理的荷瘤小鼠中，γδT 细胞的细胞因子产生和细胞毒性均显著提高。此外，在用 APS 处理的荷瘤小鼠中，TNF-α和 IFN-γ水平显著升高，而 IL-10 和 TGF-β水平显著降低。总之，本研究表明 APS 可改善肠道上皮内γδT 细胞的增殖和功能，这可能是 APS 在癌症治疗中免疫调节的重要途径。
