In this study, we studied the long-term proliferation trajectory of myeloid-derived suppressor cells (MDSCs) in murine sepsis model and investigated whether swertianolin could modulate the immunosuppressive function of MDSCs. A murine sepsis model was established by cecal ligation and perforation (CLP), according to the Minimum Quality Threshold in Pre-Clinical Sepsis Studies (MQTiPSS) guidelines. The bone marrow and spleen of the mice were collected at 24 h, 72 h, 7 and 15 d after sepsis induction. The proportions of monocytic-MDSCs (M-MDSCs; CD11b⁺LY6G^-LY6C^hi) and granulocytic-MDSCs (G-MDSC, CD11b⁺ Ly6G⁺ Ly6C^low) were analyzed by flow cytometry. Then, we have investigated whether swertianolin could modulate the immunosuppressive function of MDSCs in in vitro experiments. G-MDSCs and M-MDSCs increased acutely after sepsis with high levels sustained over a long period of time. G-MDSCs were the main subtype identified in the murine model of sepsis with polymicrobial peritonitis. Furthermore, it was found that swertianolin reduced significantly interleukin-10 (IL-10), nitric oxide (NO), reactive oxygen species (ROS), and arginase production in MDSCs, while reducing MDSC proliferation and promoting MDSC differentiation into dendritic cells. Swertianolin also improved T-cell activity by blocking the immunosuppressive effect of MDSCs. Both subsets of MDSCs significantly increased in the bone marrow and spleen of the mice with sepsis, with G-MDSCs being the main subtype identified. Swertianolin effectively regulated the functions of MDSCs and reduced immune suppression.

在这项研究中，我们研究了小鼠脓毒症模型中髓源性抑制细胞 (MDSCs) 的长期增殖轨迹，并研究了獐牙菜苷是否可以调节 MDSCs 的免疫抑制功能。根据临床前脓毒症研究中的最低质量阈值 (MQTiPSS) 指南，通过盲肠结扎和穿孔 (CLP) 建立了小鼠脓毒症模型。脓毒症诱导后24 h、72 h、7、15 d采集小鼠骨髓和脾脏。单核细胞-MDSCs (M-MDSCs; CD11b ⁺ LY6G ^- LY6C ^hi ) 和粒细胞-MDSCs (G-MDSC, CD11b ⁺ Ly6G ⁺ Ly6C ^{low ) 的比例}) 通过流式细胞仪进行分析。然后，我们研究了獐牙菜苷是否可以在体外调节 MDSCs 的免疫抑制功能实验。G-MDSCs和M-MDSCs在脓毒症后急剧增加，并在很长一段时间内保持高水平。G-MDSCs 是在多微生物腹膜炎小鼠败血症模型中发现的主要亚型。此外，发现獐牙菜苷显着降低 MDSCs 中白细胞介素 10 (IL-10)、一氧化氮 (NO)、活性氧 (ROS) 和精氨酸酶的产生，同时减少 MDSC 增殖并促进 MDSC 分化为树突状细胞。Swertianolin 还通过阻断 MDSC 的免疫抑制作用来提高 T 细胞活性。MDSCs 的两个亚型在脓毒症小鼠的骨髓和脾脏中显着增加，其中 G-MDSCs 是主要的亚型。獐牙菜素有效调节 MDSC 的功能并降低免疫抑制。