*Department of General Surgery, Jinling Hospital, Nanjing University, School of Medicine; and †Intensive Care Unit, Affiliated Second Hospital of Southeast University, Nanjing, China.
Shock. 2014 Mar;41(3):250-5. doi: 10.1097/SHK.0000000000000091.
Codonopsis pilosula polysaccharide (CPPS) isolated from one of the Chinese herbs is known to have a variety of immunomodulatory activities. However, it is not clear whether CPPS can exert an effect on the immune functions of regulatory T cells (Tregs). This study was carried out to investigate the effect of CPPS on the immune function of peripheral blood Tregs in sepsis induced by cecal ligation and puncture (CLP).
BALB/c mice were randomly divided into five groups: sham group, CLP group, CLP with CPPS (40, 100, and 250 mg/kg) treatment group, and they were killed on days 1, 2, 3, and 4 after CLP, respectively, with eight animals at each time point. Magnetic microbeads were used to isolate peripheral blood Tregs and CD4 T cells. Phenotypes of Tregs, such as Toll-like receptor 4 (TLR4) and Foxp3, were analyzed by flow cytometry, and coculture medium cytokines levels were determined with enzyme-linked immunosorbent assay. The levels of TLR4 and the expression of Foxp3 in the Treg from CLP group were markedly increased in comparison to the sham group. Administration of CPPS could significantly decrease the TLR4 level and inhibited the expression of Foxp3 on Tregs in sepsis mice. At the same time, proliferative activity and expression of interleukin 2 and interleukin 2Rα on CD4 T cells were restored. In contrast, anti-TLR4 antibody could block the effect of CPPS on Treg immune function.
Codonopsis pilosula polysaccharide might suppress excessive Tregs, at least in part, via TLR4 signaling on Tregs and trigger a shift of TH2 to TH1 with activation of CD4 T cells in sepsis induced by CLP.
党参多糖（CPPS）是从一种中草药中分离出来的，已知具有多种免疫调节活性。然而，目前尚不清楚 CPPS 是否能对调节性 T 细胞（Tregs）的免疫功能产生影响。本研究旨在探讨 CPPS 对盲肠结扎穿孔（CLP）诱导的脓毒症外周血 Tregs 免疫功能的影响。
BALB/c 小鼠随机分为五组：假手术组、CLP 组、CPPS（40、100 和 250mg/kg）治疗组，分别于 CLP 后第 1、2、3、4 天处死，每组 8 只。采用磁珠分离外周血 Tregs 和 CD4 T 细胞。采用流式细胞术分析 Tregs 的表型，如 Toll 样受体 4（TLR4）和 Foxp3，用酶联免疫吸附试验测定共培养培养基细胞因子水平。与假手术组相比，CLP 组 Treg 中的 TLR4 水平和 Foxp3 表达明显升高。CPPS 给药可显著降低 TLR4 水平，并抑制脓毒症小鼠 Tregs 中 Foxp3 的表达。同时，CD4 T 细胞的增殖活性和白细胞介素 2 和白细胞介素 2Rα 的表达得到恢复。相反，抗 TLR4 抗体可阻断 CPPS 对 Treg 免疫功能的影响。
党参多糖可能通过 TLR4 信号通路抑制 Tregs 过度激活，至少部分通过 TLR4 信号通路抑制 Tregs，在 CLP 诱导的脓毒症中触发 TH2 向 TH1 的转变，并激活 CD4 T 细胞。
