Tc17 cells are associated with cigarette smoke‐induced lung inflammation and emphysema

Abstract

Background and objective: Some types of T lymphocytes, especially cytotoxic T-cells (Tc1) and T-helper (Th17) cells, play a pivotal role in cigarette smokeinduced lung diseases. However, whether Tc17 cells are involved remains largely unknown.We investigated Tc17 involvement using a cigarette smoke-exposure model. Methods: Groups of mice were exposed to cigarette smoke or filtered air. At weeks 2, 8, 12 and 24, mice were sacrificed to observe histological changes by HE stain and/or immunohistochemical staining.The frequency of T cell subsets in the lung and spleen were detected by flow cytometry. In addition, the expression levels of T cellrelated factors were measured by real-time polymerase chain reaction or enzyme-linked immunosorbent assay. Results: Cigarette smoke caused substantial inflammatory cell infiltration and led to emphysema. Cigarette smoke exposure promoted the expression of interferon-gamma (IFN)-γ and interleukin (IL)-17A at the messenger ribonucleic acid and protein levels. In addition to Tc1 and Th17 cells, pulmonary and splenic Tc17 cells increased, which was accompanied by the upregulation of cytokines IL-6, transforming growth factor beta (TGF)-β) and transcriptional factors Stat3 and RAR-related orphan receptor gamma. Compared with untreated mice, γH2AX-positive cells were more frequently observed in mice exposed to cigarette smoke. Conclusions: Long-term cigarette smoke exposure induced Tc17 cell expansion both locally and distally, which was associated with emphysema and deoxyribonucleic acid damage. As an important source of IL-17A, this T cell subset may be a potential target for chronic obstructive pulmonary disease therapy.

IL-23 Is Essential for the Development of Elastase-Induced Pulmonary Inflammation and Emphysema

“…It has been shown that the numbers of Tc17 cells in the lung were increased in patients with COPD (11). Zhou et al reported that long-term cigarette smoke exposure induced Tc17 cell expansion(44). In the present study, IL-17A + CD8 + T cells in the lungs of control-IgG treated mice tended to be increased following PPE instillation, but treatment with anti-IL-23p40 did not affect the numbers of these T cells.…”

Impacts of cigarette smoking on immune responsiveness: Up and down or upside down?

“…A study on BAL from mice, which were exposed to tobacco smoke for at least six months, showed that the number of Th1 and Th17 cells was significantly elevated [31]. Mice with emphysema had an increased expression of Th1-type cytokine IFN-γ and Th17-type IL-17A [32, 33] and/or augmented numbers of Th17/Tc17 and Tc1 cells [33, 34]. Therefore, both murine experiments and human studies suggest that increases in Th1 and Th17 cell subsets are associated with pulmonary inflammation as a result of cigarette smoke exposure (CSE).…”

Cigarette Smoke Disturbs the Survival of CD8+ Tc/Tregs Partially through Muscarinic Receptors-Dependent Mechanisms in Chronic Obstructive Pulmonary Disease

“…Cigarette smoke-induced pulmonary inflammation, such as chronic obstructive pulmonary disease (COPD), is the fourth leading cause of death worldwide [ 1 – 3 ]. Many lines of evidence indicate that adaptive immunity plays important roles in the development of COPD, and the systemic inflammation may be a result of overspill of inflammatory mediators from the lungs [ 4 ].…”