Zhu Jianbo, Liu Xiaoying, Wang Wenxia, Ouyang Xiuhe, Zheng Wentao, Wang Qingyuan
Department of Internal Respiratory, Binzhou People's Hospital, Binzhou, Shandong 256610, P.R. China.
Department of Internal Neurology, Binzhou People's Hospital, Binzhou, Shandong 256610, P.R. China.
Exp Ther Med. 2017 Jul;14(1):714-722. doi: 10.3892/etm.2017.4519. Epub 2017 May 29.
Alteration of the careful balance of the ratio of Th1/Th2 cell subsets impacts immune function and plays an important role in the pathogenesis of asthma. There is little research on the impact of changes on the balance of the regulatory T (Treg)/Th17 subset ratio and its possible repercussions for asthma. This investigation used a murine model of asthma to measure the expression levels of Treg and Th17 cells and the levels of their transcription factors Foxp3 and retinoic acid receptor-related orphan nuclear receptor (ROR)γt in bronchial asthma while assessing indexes of airway inflammation. Thirty female SPF BALB/c mice were divided into three equally numbered groups: a normal control, an asthma and a dexamethasone treatment group. All the airway inflammation indexes measured were more prominent in the asthma group and less so in the control group. The percentage of the lymphocyte subset CD4CD25Foxp3 cells in the CD4 cells in the asthma group was significantly lower than that in the normal control group (P<0.01). The percentage of the lymphocyte subset CD4IL-17 cells in the CD4 cells in the asthma group was significantly higher than that in the normal control group (P<0.01). The ratio of CD4CD25Foxp3 cells/CD4IL-17 cells in the asthma group decreased compared with that in the normal control group (P<0.01). The expression level of Foxp3 of the mice in the asthma group was significantly lower than that in the control group (P<0.01). The expression intensity of RORγt in the asthma group was higher than that in the normal control group (P<0.01). Finally, the Foxp3/RORγt protein expression ratio in the asthma group was significantly lower than that in the normal control group (P<0.01). The Foxp3/RORγt protein expression ratio and the airway responsiveness were negatively correlated. The average levels of inflammation markers in the dexamethasone group were intermediate between the other groups. During the course of bronchial asthma the unbalanced expression of Treg and Th17 affects mostly the expression of Foxp3/RORγt, leading to inflammation of the airways. Dexamethasone may inhibit airway inflammation by regulating the balance between Treg and Th17.
Th1/Th2细胞亚群比例的精细平衡发生改变会影响免疫功能，并在哮喘发病机制中起重要作用。关于调节性T（Treg）/Th17亚群比例变化的影响及其对哮喘可能产生的后果，相关研究较少。本研究采用小鼠哮喘模型，在评估气道炎症指标的同时，检测支气管哮喘中Treg和Th17细胞的表达水平及其转录因子叉头框蛋白3（Foxp3）和维甲酸受体相关孤儿核受体（ROR）γt的水平。将30只雌性无特定病原体（SPF）BALB/c小鼠平均分为三组：正常对照组、哮喘组和地塞米松治疗组。所测的所有气道炎症指标在哮喘组中更为突出，而在对照组中则较轻。哮喘组CD4细胞中淋巴细胞亚群CD4⁺CD25⁺Foxp3⁺细胞的百分比显著低于正常对照组（P<0.01）。哮喘组CD4细胞中淋巴细胞亚群CD4⁺IL-17⁺细胞的百分比显著高于正常对照组（P<0.01）。与正常对照组相比，哮喘组CD4⁺CD25⁺Foxp3⁺细胞/CD4⁺IL-17⁺细胞的比例降低（P<0.01）。哮喘组小鼠的Foxp3表达水平显著低于对照组（P<0.01）。哮喘组RORγt的表达强度高于正常对照组（P<0.01）。最后，哮喘组的Foxp3/RORγt蛋白表达比例显著低于正常对照组（P<0.01）。Foxp3/RORγt蛋白表达比例与气道反应性呈负相关。地塞米松组炎症标志物的平均水平介于其他两组之间。在支气管哮喘病程中，Treg和Th17的表达失衡主要影响Foxp3/RORγt的表达，导致气道炎症。地塞米松可能通过调节Treg和Th17之间的平衡来抑制气道炎症。
