Enhanced activation of circulating plasmacytoid dendritic cells in patients with Chronic Obstructive Pulmonary Disease and experimental smoking-induced emphysema

• Published in: Clinical immunology (Orlando, Fla.) Vol. 195; pp. 107 - 118
• Main Authors: Qiu, Shi-lin, Kuang, Liang-jian, Tang, Qi-ya, Duan, Min-chao, Bai, Jing, He, Zhi-yi, Zhang, Jian-quan, Li, Mei-hua, Deng, Jing-min, Liu, Guang-nan, Zhong, Xiao-ning
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2018
• Subjects: COPD; IFN-γ producing CD8+ T cells; IL-17-producing CD8+ T cells; Plasmacytoid dendritic cells(pDCs); Smoking mouse model of emphysema; Smoking mouse model of emphysema; IL-17-producing CD8+T cells; IFN-γ producing CD8+T cells; Plasmacytoid dendritic cells(pDCs); COPD; IL-17-producing CD8(+)T cells; IFN-γ producing CD8(+)T cells
• ISSN: 1521-6616; 1521-7035; 1521-7035
• DOI: 10.1016/j.clim.2017.11.003

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. •Circulating pDCs in patients with COPD and in experimental smoking mouse model of emphysema exhibited an enhanced activation phenotype.•IFN-γ producing CD8+T cells (Tc1) and IL-17-producing CD8+T cells (Tc17) both were exaggerated in patients with COPD and in mice exposed to cigarette smoke.•Cigarette smoke directly promoted pDCs maturation and the secretion of a series pro-inflammatory cytokine in vitro.•Cigarette smoke extract treated pDCs were sufficient to induced differentiation of IFN-γ producing CD8+T cells and IL-17-producing CD8+T cells by mouse naïve CD8+T cells in vitro.