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Enhanced activation of circulating plasmacytoid dendritic cells in patients with Chronic Obstructive Pulmonary Disease and experimental smoking-induced emphysema
Clinical Immunology ( IF 8.6 ) Pub Date : 2017-11-08 , DOI: 10.1016/j.clim.2017.11.003
Shi-lin Qiu , Liang-jian Kuang , Qi-ya Tang , Min-chao Duan , Jing Bai , Zhi-yi He , Jian-quan Zhang , Mei-hua Li , Jing-min Deng , Guang-nan Liu , Xiao-ning Zhong

Plasmacytoid dendritic cells (pDCs) are key cells bridging the innate with adaptive immunity. However, the phenotypic characteristics of circulating pDCs and its role in smoking related-Chronic Obstructive Pulmonary Disease (COPD) remain largely unknown. The aim of this study was analyzed the phenotype of circulating pDCs and the expression of IFN-γ producing CD8+ T cells and IL-17-producing CD8+ T cells in patients with COPD by using multi-colour flow cytometry. The cytokine profiles in peripheral blood from all subjects were measured by ELISA. The influence of cigarette smoke on pDCs was evaluated in an experimental mouse model of emphysema. Circulating pDCs in patients with COPD and in mice exposed to cigarette smoke expressed high levels of co-stimulatory molecules CD40 or CD86 accompanied by exaggerated IFN-γ producing CD8+ T cells and IL-17-producing CD8+ T cells. In vitro, cigarette smoke directly promoted pDCs maturation and release of IFN-α, IL-6 and IL-12, subsequently inducing differentiation of IFN-γ producing CD8+ T cells and IL-17-producing CD8+ T cells from mouse naïve CD8+ T cells. These data suggested that circulating pDCs display an enhanced activation phenotype in patients with COPD and in experimental smoking mouse model of emphysema, which might contribute to exaggerated IFN-γ producing CD8+ T and IL-17-producing CD8+ T cell-mediated immune responses.



中文翻译:

慢性阻塞性肺疾病和实验性吸烟引起的肺气肿患者循环浆细胞样树突状细胞的活化增强

浆细胞样树突状细胞(pDC)是通过适应性免疫桥接先天的关键细胞。但是,循环pDC的表型特征及其在与吸烟相关的慢性阻塞性肺疾病(COPD)中的作用仍然未知。本研究的目的是分析循环pDC的表型以及产生IFN-γ的CD8 +  T细胞和产生IL-17的CD8 +的表达。 通过多色流式细胞术检测COPD患者的T细胞。通过ELISA测量来自所有受试者的外周血中的细胞因子谱。在实验性肺气肿小鼠模型中评估了香烟烟雾对pDC的影响。COPD患者和暴露于香烟烟雾中的小鼠中的循环pDCs表达高水平的共刺激分子CD40或CD86,并伴有产生IFN-γ的CD8 +  T细胞和产生IL-17的CD8 +  T细胞的过度表达。在体外,香烟烟雾直接促进pDC的成熟并释放IFN-α,IL-6和IL-12,随后诱导 从幼稚CD8分化产生IFN-γ的CD8 +  T细胞和产生IL-17的CD8 + T细胞+  T细胞。这些数据表明,在患有COPD的患者和实验性吸烟的肺气肿小鼠模型中,循环中的pDCs表现出增强的激活表型,这可能有助于夸大产生IFN-γ的CD8 +  T和产生IL-17的CD8 +  T细胞介导的免疫反应。

更新日期:2017-11-08
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