Abstract：
The polysaccharide, RGP2, was isolated from Russula griseocarnosa and its immunostimulatory effects were confirmed in cyclophosphamide (CTX)-induced immunosuppressed mice. Following purification via chromatography, structural analysis revealed that RGP2 had a molecular weight of 11.82 kDa and consisted of glucose (Glc), galactose (Gal), mannose, glucuronic acid and glucosamine. Bond structure analysis and nuclear magnetic resonance characterization confirmed that the main chain of RGP2 was formed by →6)-β-D-Glcp-(1→, →3)-β-D-Glcp-(1→ and →6)-α-D-Galp-(1→, which was substituted at O-3 of →6)-β-D-Glcp-(1→ by β-D-Glcp-(1→. RGP2 was found to ameliorate pathological damage in the spleen and enhance immune cell activity in immunosuppressed mice. Based on combined multiomics analysis, RGP2 altered the abundance of immune-related microbiota (such as Lactobacillus, Faecalibacterium, and Bacteroides) in the gut and metabolites (uridine, leucine, and tryptophan) in the serum. Compared with immunosuppressed mice, RGP2 also restored the function of antigen-presenting cells, promoted the polarization of macrophages into the M1 phenotype, positively affected the differentiation of helper T cells, and inhibited regulatory T cell differentiation through the protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) pathway, ultimately exerting an immune boosting function. Overall, our findings highlight therapeutic strategies to alleviate CTX-induced immunosuppression in a clinical setting.
摘要：
多糖，RGP2分离自Russulagriseocarnosa，并在环磷酰胺（CTX）诱导的免疫抑制小鼠中证实了其免疫刺激作用。通过色谱法纯化后，结构分析表明，RGP2的分子量为11.82kDa，由葡萄糖（Glc）组成，半乳糖（Gal），甘露糖,葡萄糖醛酸和葡糖胺。键结构分析和核磁共振表征证实，RGP2的主链由→6）-β-D-Glcp-（1→，→3)-β-D-Glcp-(1→和→6)-α-D-Galp-(1→，在→6的O-3处被取代）-β-D-Glcp-（1→被β-D-Glcp-（1→。发现RGP2可改善免疫抑制小鼠脾脏的病理损伤并增强免疫细胞活性。基于联合的多组学分析，RGP2改变了免疫相关微生物群的丰度（如乳杆菌，粪杆菌,和拟杆菌)在肠道和代谢物(尿苷，亮氨酸,和色氨酸）在血清中。与免疫抑制小鼠相比，RGP2还恢复了抗原呈递细胞的功能，促进巨噬细胞极化为M1表型，积极影响辅助性T细胞的分化，并通过蛋白激酶B（AKT）/雷帕霉素机制靶点（mTOR）途径抑制调节性T细胞分化，最终发挥免疫增强功能。总的来说,我们的研究结果强调了在临床环境中缓解CTX诱导的免疫抑制的治疗策略.
