C3a-C3aR信号通路对正常儿童Treg/Th17免疫平衡的影响

Effects of C3a-C3aR signaling pathway on the balance of Treg/Th17 cells in healthy children

目的探讨补体C3a-C3a受体(C3aR)信号通路对正常儿童外周血Treg/Th17免疫平衡的影响,以期为进一步研究该通路在相关疾病中的作用提供实验依据。方法健康体检儿童17例,其中男性10例,女性7例,平均年龄6.8岁。收取空腹外周血3 ml,提取外周血单个核细胞(PBMC),分为3组:1)正常对照组;2)人重组C3a处理组(C3a组);3)人重组C3a及C3a受体拮抗剂处理组(C3a+C3aRA组)。经过培养后应用流式细胞术分别检测各组中Treg细胞和Th17细胞占CD4+T细胞的百分比,并比较各组间Treg/Th17的比值。结果与正常对照组比较,C3a组Th17细胞比例升高(P<0.01),Treg/Th17的比值明显降低(P<0.01),Treg细胞比例有下降趋势,但无明显统计学差异(P>0.05);与C3a组比较,C3a+C3aRA组Th17细胞比例降低(P<0.05),Treg/Th17的比值明显升高(P<0.05),Treg细胞比例有上升趋势,但无统计学差异(P>0.05);而C3a+C3aRA组较正常对照组Th17细胞、Treg细胞比例以及Treg/Th17的比值均无统计学差异(P>0.05)。结论 C3a-C3aR信号通路可能介导正常生理状态下儿童外周血中Th17细胞活化,同时参与调控正常儿童Treg/Th17细胞免疫平衡。

The Treg/Th17 balance plays a crucial role in the regulation of immune responses. This study aimed to investigate the effects of C3a-C3aR（C3a receptor） signaling pathway on the Treg/Th17 balance in peripheral blood mononuclear cells（PBMCs） of healthy children. Total of 17 healthy children were enrolled in our study. PBMCs were isolated from healthy donors and divided into three groups： control group, C3a-treated group,C3a＋C3a receptor antagonists（C3aRA）-treated group. The percentage of Treg and Th17 cells in PBMCs of each group was detected by flow cytometry, and then Treg/Th17 ratio was calculated. We found that Th17 cells were remarkably increased（P〈 0.01） and the Treg/Th17 ratio was dramatically decreased（P〈 0.01） in the C3a-treated group compared with the control group, while there was no significant difference in the proportion of Treg cells between the two groups（P 0.05）. Th17 cells were markedly decreased（P〉 0.05） and the Treg/Th17 ratio was profoundly increased（P〈 0.05） in the C3a＋C3aRA-treated group in contrast to the C3a-treated group, whereas,there was no difference in the proportion of Treg cells between the two groups（P 〉0.05）. Th17 cells, Treg cells and Treg/Th17 ratio showed no significant difference in the C3a＋C3aRA-treated groups versus the control group（P 〉0.05）. In conclusion, C3a-C3 aR signaling pathway is involved in the activation of Th17 cells and might participate in the regulation of Treg/Th17 balance in PBMCs in healthy children.