哮喘小鼠CCR4/TARC信号轴对Treg/Th17细胞平衡的调控研究

Regulation of TCR/Th17 cell infiltration into lung by CCR4/TARC signal axis in mouse asthma model

目的探讨CC类趋化因子受体4(CCR4)/胸腺激活调节趋化因子(TARC)信号轴对哮喘小鼠调节性T细胞(Treg)/辅助性T细胞17(Th17)细胞的调控作用。方法选择广西医科大学动物实验中心BALB/C雌性小鼠20只作为研究对象,随机选择10只为哮喘组,另10只为对照组。比较两组小鼠肺组织病理学改变、炎症细胞浸润评分和Treg、Th17、CCR4、IL-17A、TARC表达,分析炎症细胞浸润评分、Th17细胞与支气管肺泡灌洗液(BALF)内TARC的相关性。结果哮喘组炎症细胞浸润评分高于对照组,差异有统计学意义(P<0.01)。与对照组比较,哮喘组肺内、外周血中的Treg/Th17细胞比值更低,差异有统计学意义(P<0.05)。哮喘组和对照组肺内、外周血中的CCR4在Treg、Th17细胞表达水平比较差异无统计学意义(P>0.05)。与对照组比较,哮喘组小鼠BALF中TARC的浓度更高,差异有统计学意义(P<0.05)。哮喘组肺内炎症细胞浸润评分与BALF内TARC浓度呈正相关(r=0.773,P<0.05)。哮喘组肺内Th17细胞与BALF内TARC浓度呈正相关(r=0.786,P=0.002)。结论Treg/Th17细胞比值变化与哮喘肺内炎症的发生、发展有密切相关,而CCR4/TARC信号轴可能通过对Th17的调控参与炎症向肺内的浸润。

Objective To explore the role of CC chemokine receptor 4(CCR4)/thymocyte activation-regulating chemokine(TARC)signal axis in regulating T cells(Treg)/helper T cells 17(Th17)cells in asthmatic mice.Methods Twenty SPF BALB/C female mice from the Animal Experiment Center of Guangxi Medical University were selected as the research subjects,and randomly divided into asthma group and control group,10 mice in each.In the asthma group chicken ovalbumin(OVA)was used for sensitization and stimulation and in the control group phosphate buffered saline(PBS)was used.The two groups were compared in terms of lung histopathological changes,inflammatory cell infiltration score,Treg,Th17,CCR4,IL-17 A,TARC expression,and the correlation between inflammatory cell infiltration score,Th17 cells and TARC in bronchoalveolar lavage fluid(BALE)was analyzed.Results The inflammatory cell infiltration score in the asthma group was significantly higher than that in the control group(P<0.01).The ratio of Treg/Th17 cells in lung and peripheral blood of asthma group was significantly lower than that of control group(P<0.05).Compared with the control group,the expression of CCR4 in the lung and peripheral blood of asthma group in Treg and Th17 cells was not statistically significant(P>0.05).The concentration of TARC in BALF of asthmatic mice was significantly higher than that of the control group(P<0.05).The inflammatory cell infiltration score in the lungs of asthma group was positively correlated with the TARC concentration in BALF(r=0.773,P<0.05).The number of Th17 cells in the asthma group was positively correlated with the TARC concentration in BALF as well(r=0.786,P=0.002).Conclusion The change of Treg/Th 17 cell ratio is closely related to the occurrence and development of asthma pulmonary inflammation.The CCR4/TARC signal axis of asthmatic mice may play a regulatory role in the infiltration of Th17 cells into the lung.