Cigarette smoke exposure promotes differentiation of CD4+T cells toward Th17 cells by CD40-CD40L costimulatory pathway in mice

Abstract

Yi Liang,1 Ying Shen,2 Liangjian Kuang,1 Guang Zhou,1 Longju Zhang,1 Xiaoning Zhong,1 Jianquan Zhang,1 Jifeng Liu1 1Department of Respiratory Medicine, The First Affiliated Hospital of Guangxi Medical University, 2Division of General Practice, General Practice School of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China Purpose: 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.Methods: 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.Results: 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.Conclusion: 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. Keywords: cigarette smoke extract, BMDC, CD4+IL-17+ T cell, CD40–CD40L pathway, IL-17A, IL-27

Keywords

• Cigarette smoke extract
• BMDC
• CD4+IL-17+T cell
• CD40-CD40L pathway