Liang Yi, Shen Ying, Kuang Liangjian, Zhou Guang, Zhang Longju, Zhong Xiaoning, Zhang Jianquan, Liu Jifeng
Department of Respiratory Medicine, The First Affiliated Hospital of Guangxi Medical University.
Division of General Practice, General Practice School of Guangxi Medical University, Nanning, Guangxi, People's Republic of China.
Int J Chron Obstruct Pulmon Dis. 2018 Mar 21;13:959-968. doi: 10.2147/COPD.S155754. eCollection 2018.
This study aimed to investigate the impact of cigarette smoke exposure upon CD40-CD40L ligation between bone marrow-derived dendritic cells (BMDCs)and CD4T cells, and to examine the effects of cigarette smoke exposure upon differentiation of CD4T cells toward Th17 cells through blockade of CD40-CD40L pathway in mice.
The study was processed in vivo and in vitro. In vivo, Th17 cells, CD40, interleukin (IL)-17A, and IL-27 in the lung tissues were quantified and compared between mice with and without cigarette smoke exposure. In vitro, Th17 cells, IL-17A, and IL-27 yielded by multiple cell cultivations in which BMDCs from mice with or without cigarette smoke exposure were fostered with CD4 T cells from healthy mice spleens in the presence of antagonistic CD40 antibody and/or cigarette smoke extract (CSE) were quantified and compared. The flow cytometry was used to detect expressions of Th17 cells and CD40, and the liquid chip was used to detect levels of IL-17A and IL-27.
Both in vivo exposed to cigarette smoke and in vitro to CSE, CD40 expressions noticeably escalated on the surfaces of BMDCs. The presence of Th17 cells, IL-17A, and IL-27 in the lung tissues prominently increased in mice exposed to cigarette smoke. The in vitro culture of CD4 T cells and BMDCs significantly enhanced the differentiation of CD4 T cells toward Th17 cells and secretions of IL-17A and IL-27 in the case that BMDCs were produced from mice exposed to cigarette smoke or the culture occurred in the presence of CSE. Usage of antagonistic CD40 antibody evidently reduced the number of Th17 cells, IL-17A, and IL-27 that increased due to cigarette smoke exposure.
The CD40-CD40L ligation is associated with the quantities of Th17 cells and relevant cytokines in the context of cigarette smoke exposure. Reducing the number of Th17 cells via the usage of antagonistic CD40 antibody can be an inspiration for pursuing a novel therapeutic target for immune inflammation in COPD.
本研究旨在探讨香烟烟雾暴露对骨髓来源的树突状细胞（BMDCs）与CD4 T细胞之间CD40-CD40L连接的影响，并通过阻断小鼠CD40-CD40L途径来研究香烟烟雾暴露对CD4 T细胞向Th17细胞分化的影响。
本研究采用体内和体外实验方法。在体内，对暴露于香烟烟雾和未暴露于香烟烟雾的小鼠肺组织中的Th17细胞、CD40、白细胞介素（IL）-17A和IL-27进行定量并比较。在体外，对来自暴露于香烟烟雾和未暴露于香烟烟雾的小鼠的BMDCs与健康小鼠脾脏中的CD4 T细胞在存在抗CD40抗体和/或香烟烟雾提取物（CSE）的情况下进行多次细胞培养所产生的Th17细胞、IL-17A和IL-27进行定量并比较。采用流式细胞术检测Th17细胞和CD40的表达，采用液相芯片检测IL-17A和IL-27的水平。
无论是在体内暴露于香烟烟雾还是在体外暴露于CSE，BMDCs表面的CD40表达均明显升高。暴露于香烟烟雾的小鼠肺组织中Th17细胞、IL-17A和IL-27的含量显著增加。在由暴露于香烟烟雾的小鼠产生BMDCs或在存在CSE的情况下进行培养的情况下，CD4 T细胞与BMDCs的体外培养显著增强了CD4 T细胞向Th17细胞的分化以及IL-17A和IL-27的分泌。使用抗CD40抗体明显减少了因香烟烟雾暴露而增加的Th17细胞、IL-17A和IL-27的数量。
在香烟烟雾暴露的情况下，CD40-CD40L连接与Th17细胞及相关细胞因子的数量有关。通过使用抗CD40抗体减少Th17细胞数量可为寻求慢性阻塞性肺疾病免疫炎症的新治疗靶点提供思路。
