Dendritic cells induce Tc1 cell differentiation via the CD40/CD40L pathway in mice after exposure to cigarette smoke

• Published in: American journal of physiology. Lung cellular and molecular physiology Vol. 311; no. 3; pp. L581 - L589
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.09.2016
• Subjects: Animals; CD40 Antigens - physiology; CD40 Ligand - physiology; CD8-Positive T-Lymphocytes; Cell Differentiation; Cells; Cells, Cultured; Chronic obstructive pulmonary disease; Cigarettes; Cytokines - biosynthesis; Cytokines - genetics; Dendritic Cells - physiology; Emphysema; Experiments; Lung - immunology; Lung - metabolism; Lung - pathology; Lymphocyte Count; Mice, Inbred C57BL; Mice, Knockout; Nicotiana - adverse effects; Pulmonary Emphysema - etiology; Pulmonary Emphysema - immunology; Pulmonary Emphysema - metabolism; Rodents; Signal Transduction; Smoke - adverse effects; Smoking - adverse effects; T-Box Domain Proteins - genetics; T-Box Domain Proteins - metabolism; CD40; Tc1 cell; cigarette smoke; dendritic cell; emphysema
• ISSN: 1040-0605; 1522-1504; 1522-1504
• DOI: 10.1152/ajplung.00002.2016

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.