Cigarette smoke exposure promotes differentiation of CD4(+) T cells toward Th17 cells by CD40-CD40L costimulatory pathway in mice.
Cigarette smoke exposure promotes differentiation of CD4(+) T cells toward Th17 cells by CD40-CD40L costimulatory pathway in mice.
复制标题
香烟烟雾暴露通过 CD40-CD40L 共刺激途径促进小鼠 CD4( ) T 细胞向 Th17 细胞分化
DOI：
10.2147/copd.s155754
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发表时间：
2018
影响因子：
2.8
通讯作者：
Liu J
中科院分区：
文献类型：
--
作者：
Liang Y;Shen Y;Kuang L;Zhou G;Zhang L;Zhong X;Zhang J;Liu J
本研究旨在探讨香烟烟雾暴露对骨髓源性树突状细胞（BMDC）和 CD4+T 细胞之间 CD40-CD40L 连接的影响，并通过阻断小鼠 CD40-CD40L 通路来研究香烟烟雾暴露对 CD4+T 细胞向 Th17 细胞分化的影响。该研究在体内和体外进行。在体内，对有和没有接触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 进行定量和比较。在体外，对通过多重细胞培养产生的 Th17 细胞、IL-17A 和 IL-27 进行定量和比较，其中在拮抗性 CD40 抗体和/或香烟烟雾提取物 (CSE) 存在的情况下，将来自有或没有接触香烟烟雾的小鼠的 BMDC 与来自健康小鼠脾脏的 CD4+ T 细胞一起培养。采用流式细胞术检测Th17细胞、CD40的表达,采用液相芯片检测IL-17A、IL-27的水平。无论是体内暴露于香烟烟雾还是体外暴露于 CSE，BMDC 表面的 CD40 表达均显着升高。暴露于香烟烟雾的小鼠肺组织中 Th17 细胞、IL-17A 和 IL-27 的存在显着增加。在暴露于香烟烟雾的小鼠中产生BMDC或在存在CSE的情况下进行培养的情况下，CD4+T细胞和BMDC的体外培养显着增强CD4+T细胞向Th17细胞的分化以及IL-17A和IL-27的分泌。使用拮抗性 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。 CD40-CD40L 连接与香烟烟雾暴露背景下 Th17 细胞和相关细胞因子的数量有关。通过使用拮抗性 CD40 抗体减少 Th17 细胞的数量可以为寻找 COPD 免疫炎症的新治疗靶点提供灵感。
This study aimed to investigate the impact of cigarette smoke exposure upon CD40–CD40L ligation between bone marrow-derived dendritic cells (BMDCs)and CD4+T cells, and to examine the effects of cigarette smoke exposure upon differentiation of CD4+T 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.