Kuang Liang-Jian, Deng Ting-Ting, Wang Qin, Qiu Shi-Lin, Liang Yi, He Zhi-Yi, Zhang Jian-Quan, Bai Jing, Li Mei-Hua, Deng Jing-Min, Liu Guang-Nan, Liu Ji-Feng, Zhong Xiao-Ning
Department of Respiratory Medicine, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China; and.
Department of Respiratory Medicine, Tenth Affiliated Hospital of Guangxi Medical University, Qinzhou, Guangxi, China.
Am J Physiol Lung Cell Mol Physiol. 2016 Sep 1;311(3):L581-9. doi: 10.1152/ajplung.00002.2016. Epub 2016 Jul 22.
Dendritic cells and CD8(+) T cells participate in the pathology of chronic obstructive pulmonary disease, including emphysema, but little is known of the involvement of the CD40/CD40L pathway. We investigated the role of the CD40/CD40L pathway in Tc1 cell differentiation induced by dendritic cells in a mouse model of emphysema, and in vitro. C57BL/6J wild-type and CD40(-/-) mice were exposed to cigarette smoke (CS) or not (control), for 24 wk. In vitro experiments involved wild-type and CD40(-/-) dendritic cells treated with CS extract (CSE) or not. Compared with the control groups, the CS mice (both wild type and CD40(-/-)) had a greater percentage of lung dendritic cells and higher levels of major histocompatability complex (MHC) class I molecules and costimulatory molecules CD40 and CD80. Relative to the CS CD40(-/-) mice, the CS wild type showed greater signs of lung damage and Tc1 cell differentiation. In vitro, the CSE-treated wild-type cells evidenced more cytokine release (IL-12/p70) and Tc1 cell differentiation than did the CSE-treated CD40(-/-) cells. Exposure to cigarette smoke increases the percentage of lung dendritic cells and promotes Tc1 cell differentiation via the CD40/CD40L pathway. Blocking the CD40/CD40L pathway may suppress development of emphysema in mice exposed to cigarette smoke.
树突状细胞和CD8(+) T细胞参与慢性阻塞性肺疾病（包括肺气肿）的病理过程，但关于CD40/CD40L途径的参与情况知之甚少。我们在肺气肿小鼠模型中及体外研究了CD40/CD40L途径在树突状细胞诱导的Tc1细胞分化中的作用。将C57BL/6J野生型和CD40(-/-)小鼠暴露于香烟烟雾（CS）或不暴露（对照）24周。体外实验涉及用CS提取物（CSE）处理或不处理的野生型和CD40(-/-)树突状细胞。与对照组相比，CS小鼠（野生型和CD40(-/-)）的肺树突状细胞百分比更高，主要组织相容性复合体（MHC）I类分子以及共刺激分子CD40和CD80水平更高。相对于CS CD40(-/-)小鼠，CS野生型小鼠表现出更明显的肺损伤和Tc细胞分化迹象。在体外，与经CSE处理的CD40(-/-)细胞相比，经CSE处理的野生型细胞释放更多细胞因子（IL-12/p70）并促进Tc1细胞分化。暴露于香烟烟雾会增加肺树突状细胞百分比，并通过CD40/CD40L途径促进Tc1细胞分化。阻断CD40/CD40L途径可能会抑制暴露于香烟烟雾的小鼠肺气肿的发展。
