Yang Xia, Zhang Jing-Hong, Zhang Jian-Feng, Lin Hua, Chen Wei, Xiang Li, Li Chao-Qian
Department of Emergency, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi, China.
The Guangxi Talent Highland for Emergency and Rescue Medicine, Guangxi Colleges and Universities Key Laboratory of Emergency Medicine Research, Nanning 530021, Guangxi, China.
Iran J Allergy Asthma Immunol. 2017 Dec;16(6):511-519.
Recent studies suggest that imbalances in the ratios of CD4+ T helper cell subsets, T helper-17 (Th17) and regulatory T (Treg) cells play a crucial role in the pathogenesis of acute lung injury (ALI). However, studies of the imbalance of Th17/Treg in paraquat (PQ)-induced ALI have not been reported. Therefore, we investigated whether the ratio of Th17/Treg cells in a mouse model of PQ-induced ALI contributes to pathogenesis of ALI. Male Kunming mice were randomly treated with saline (control group) or PQ (PQ-poisoned (PQP) group); mice were sacrificed at either 12 hours (PQP-12h) or 24 hours (PQP-24h and control) post-treatment. Hematoxylin-eosin and TUNEL staining procedures were performed to examine inflammation and apoptosis. The presence of Th17 and Treg cells was measured by flow cytometry; the expression of putative Th17 cytokines and transcription factors was measured by ELISA and western blot analysis. Compared with control mice, lung inflammation and apoptosis were dramatically increased in PQP mice at 12 and 24 hours after poisoning. In addition, poisoned mice displayed significant increases in the presence of CD4+IL-17+ T cells (Th17) and in the expression of IL-17A and IL-17, as measured by flow cytometry and western blot assays. This increase was most notable after 24 hours of PQ exposure. Furthermore, poisoned mice displayed marked decreases in the presence of CD4+CD25+Foxp3+ T cells (Treg) and in the expression of IL-35 and the transcription factor Foxp3. These results suggest that an imbalanced ratio of Th17/Treg cells may contribute to the pathogenesis of PQ-induced ALI.
近期研究表明，CD4+辅助性T细胞亚群、辅助性T细胞17（Th17）和调节性T（Treg）细胞的比例失衡在急性肺损伤（ALI）的发病机制中起关键作用。然而，关于百草枯（PQ）诱导的ALI中Th17/Treg失衡的研究尚未见报道。因此，我们研究了PQ诱导的ALI小鼠模型中Th17/Treg细胞比例是否与ALI的发病机制有关。雄性昆明小鼠随机接受生理盐水处理（对照组）或PQ处理（PQ中毒（PQP）组）；在处理后12小时（PQP - 12h）或24小时（PQP - 24h和对照组）处死小鼠。进行苏木精 - 伊红和TUNEL染色程序以检查炎症和细胞凋亡。通过流式细胞术检测Th17和Treg细胞的存在；通过ELISA和蛋白质印迹分析检测假定的Th17细胞因子和转录因子的表达。与对照小鼠相比，中毒后12小时和24小时，PQP小鼠的肺部炎症和细胞凋亡显著增加。此外，通过流式细胞术和蛋白质印迹分析测定，中毒小鼠的CD4 + IL - 17 + T细胞（Th17）的存在以及IL - 17A和IL - 17的表达显著增加。PQ暴露24小时后这种增加最为明显。此外，中毒小鼠的CD4 + CD25 + Foxp3 + T细胞（Treg）的存在以及IL - 35和转录因子Foxp3的表达显著降低。这些结果表明，Th17/Treg细胞比例失衡可能与PQ诱导的ALI的发病机制有关。
