Abstract
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.
Highlights
Astragalus polysaccharides (APS), the main efficacious principles extracted from Astragalus membranaceus, have been proved to possess multiple immunomodulatory functions, including inhibiting the proliferation of CD4+CD25+ regulatoryT (Treg) cells [1], promoting the maturation of dendritic cells (DCs) [2], enhancing the cytostatic activity of macrophages [3], regulating the imbalance of Thl/Th2 subgroups, and differentiation of the erythroid lineage [4,5], etc
We found that APS induced significant proliferation of intestinal intraepithelial γδT cells in vitro (Figure 1B)
FasL and granzyme B (GrB) mRNA levels in γδT cells were significantly increased after treatment with APS (P < 0.01) (Figure 1E,F)
Summary
T (Treg) cells [1], promoting the maturation of dendritic cells (DCs) [2], enhancing the cytostatic activity of macrophages [3], regulating the imbalance of Thl/Th2 subgroups, and differentiation of the erythroid lineage [4,5], etc. It is regarded as a hopeful adjuvant to cancer therapy [6,7]. Due to its high molecular weight, orally administration of APS is not absorbed into the blood stream directly for functional activity. As the intestine is an important immune organ consisting of a complex cellular network [9], we, assume that enteric mucosal immune response might trigger the immune regulation of APS
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