The immunomodulatory effects of Euglena gracilis (Euglena) and its bioactive component, β-1,3-glucan (paramylon), have been clarified through various studies. However, the detailed mechanisms of the immune regulation remain to be elucidated. This study was designed not only to investigate the immunomodulatory effects but also to determine the genetic mechanisms of Euglena and β-glucan in cyclophosphamide (CCP)-induced immunosuppressed mice. The animals were orally administered saline, Euglena (800 mg/kg B.W.) or β-glucan (400 mg/kg B.W.) for 19 days, and CCP (80 mg/kg B.W.) was subsequently administered to induce immunosuppression in the mice. The mice exhibited significant decreases in body weight, organ weight, and the spleen index. However, there were significant improvements in the spleen weight and the spleen index in CCP-induced mice after the oral administration of Euglena and β-glucan. Transcriptome analysis of the splenocytes revealed immune-related differentially expressed genes (DEGs) regulated in the Euglena - and β-glucan-treated groups. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that pathways related with interleukin (IL)-17 and cAMP play significant roles in regulating T cells, B cells, and inflammatory cytokines. Additionally, Ptgs2, a major inflammatory factor, was exclusively expressed in the Euglena-treated group, suggesting that Euglena's beneficial components, such as carotenoids, could regulate these genes by influencing immune lymphocytes and inflammatory cytokines in CCP-induced mice. This study validated the immunomodulatory effects of Euglena and highlighted its underlying mechanisms, suggesting a positive contribution to the determination of phenotypes associated with immune-related diseases and the research and development of immunotherapies.

中文翻译：

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揭示眼虫对免疫抑制小鼠的免疫调节作用：转录组和通路分析。

细小眼虫（Euglena ）及其生物活性成分β-1,3-葡聚糖（裸藻淀粉）的免疫调节作用已通过各种研究得到阐明。然而，免疫调节的详细机制仍有待阐明。本研究不仅旨在研究免疫调节作用，还旨在确定眼虫和β-葡聚糖在环磷酰胺（CCP）诱导的免疫抑制小鼠中的遗传机制。给动物口服盐水、眼虫（800 mg/kg BW）或β-葡聚糖（400 mg/kg BW）19天，随后给予CCP（80 mg/kg BW）以诱导小鼠免疫抑制。小鼠的体重、器官重量和脾脏指数显着下降。然而，口服眼虫和β-葡聚糖后，CCP诱导的小鼠脾脏重量和脾脏指数有显着改善。脾细胞的转录组分析揭示了眼虫和β-葡聚糖处理组中免疫相关的差异表达基因（DEG）受到调节。基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析表明，白细胞介素（IL）-17和cAMP相关通路在调节T细胞、B细胞和炎症细胞因子中发挥重要作用。此外，Ptgs2（一种主要炎症因子）仅在眼虫治疗组中表达，这表明眼虫的有益成分（如类胡萝卜素）可以通过影响 CCP 诱导小鼠的免疫淋巴细胞和炎症细胞因子来调节这些基因。该研究验证了裸藻的免疫调节作用，并强调了其潜在机制，对免疫相关疾病相关表型的确定以及免疫疗法的研发做出了积极贡献。