Th17细胞和调节性T细胞失衡参与实验性自身免疫性脑脊髓炎的发病

Th17/Treg unbalance is involved in the pathogenesis of experimental autoimmune encephalomyelitis

目的探讨Th17细胞和调节性T细胞(Treg)失衡在实验性自身免疫性脑脊髓炎(EAE)发病过程中的作用。方法建立EAE小鼠模型,在EAE发病的不同时期运用流式细胞术检测小鼠脾脏Treg比例变化,用实时定量PCR(qRT-PCR)分别检测小鼠脾淋巴细胞Foxp3、视黄酸相关的孤儿受体γt(RoR-γt)以及脑组织IL-17 mRNA表达,ELISA检测小鼠外周血IL-6、转化生长因子β(TGF-β)及IL-17A含量变化。结果与佐剂对照组比较,CD4+CD25+Foxp3+Treg比例和Foxp3 mRNA的表达,在EAE发病初期及高峰期明显下降,而在慢性期明显升高(P<0.05);RoR-γt mRNA表达量在发病初期与佐剂对照组比较显著增加(P<0.05),而高峰期及慢性期与佐剂对照组比较则无显著差异(P>0.05)。EAE组小鼠外周血中TGF-β、IL-6浓度在发病初期和高峰期明显升高(P<0.05);随病情发展,IL-6浓度逐渐降低,在发病慢性期与佐剂对照组比较无明显差异(P>0.05),而TGF-β浓度在发病慢性期仍较高,与佐剂对照组比较明显升高(P<0.05)。EAE组小鼠外周血中IL-17A含量在EAE不同时期均有明显升高,且高峰期升高最明显(P<0.05)。结论 Th17细胞/Treg失衡参与了EAE发病过程。

Objective To investigate the role of Th17/Treg unbalance in the pathogenesis of experimental autoimmune encephalomyelitis（ EAE）. Methods EAE was modeled in mice and the number of regulatory T cells（ Tregs） in spleen of EAE mice was detected by flow cytometry. The expressions of Foxp3 and RoR-γt mRNA in the spleen of EAE mice and IL-17 mRNA in the brain of EAE mice were evaluated by real-time quantitative PCR and the levels of IL-6,TGF-β and IL-17 in the serum of EAE mice were examined by ELISA. Results Compared with control group,the number of CD4＋CD25＋Foxp3＋Tregs and the expression of Foxp3 mRNA in the spleen of EAE mice dramatically decreased in the early and peak stage of EAE（ P〈0. 05）,but increased in chronic stage of EAE（ P〈0. 05）; the RoR-γt mRNA expression from mouse spleen at the early stage of EAE was significant raised（ P〈0. 05）,but was not significantly different at the peak and chronic stage of EAE from that in control group（ P〉0. 05）. The levels of IL-6 and TGF-β in the serum of EAE group dramatically increased compared with control group（ P〈0. 05）. With the development of EAE,the level of IL-6 gradually decreased,and there was no statistical difference in the chronic stage of EAE compared with control group（ P〉0. 05）. However,the level of TGF-βwas higher than that in control group in the chronic stage of EAE（ P〈0. 05）. Compared with those in control group,the concentration of IL-17 A and the expression of IL-17 mRNA dramatically increased in different stages of EAE group,especially in peak stage（ P〈0. 05）. Conclusion Th17 /Treg unbalance may be involved in the pathogenesis of EAE.