Increased IFN-\u03b3-producing Th17/Th1 cells and their association with lung function and current smoking status in patients with chronic obstructive pulmonary disease

Weihan Xu,Yongchang Sun,Ruimin Li

doi:10.1186/s12890-019-0899-2

Abstract

BackgroundTh17 cells are believed to be important proinflammatory cells in the pathogenesis of chronic obstructive pulmonary disease (COPD). Recent evidence demonstrates that Th17 cells display substantial developmental plasticity, giving rise to Th17/Th1 cells that secret both IL-17 and IFN-γ and are more pathogenic in inflammatory diseases. The aim of this study was to examine the distribution of circulating Th17/Th1 subpopulation and its association with disease severity in patients with COPD.MethodsBlood samples were obtained from 21 never-smokers, 31 smokers with normal lung function and 83 patients with COPD. The frequencies of Th17 cells and the Th17/Th1 subset were measured using flow cytometry. Plasma concentrations of IL-6, transforming growth factor (TGF)-β1 and IL-12 were determined by ELISA. The associations of Th17/Th1 cells with lung function and smoking were evaluated.ResultsIn peripheral blood, significantly increased proportions of Th17/Th1 cells among CD4 cells and Th17 cells were found in COPD patients compared with never-smokers and smokers with normal lung function. The percentages of Th17/Th1 cells showed correlations with forced expiratory volume in 1 (FEV1) % predicted value (r = − 0.244, p < 0.05), and higher proportions of Th17/Th1 cells in GOLD stage IV patients compared with stage I patients. The percentages of Th17/Th1 cells were significantly higher in current smokers compared with ex-smoker COPD patients, and positively correlated with pack-years of smoking (r = 0.352, p < 0.01). The plasma concentrations of IL-6, TGF-β1 and IL-12 were significantly increased in patients with COPD compared with never-smokers and smokers with normal lung function.ConclusionOur results revealed correlations of proportions of IFN-γ-producing Th17/Th1 cells with lung function and smoking, suggesting that increased Th17/Th1 cells may play a role in COPD progression.

Highlights

Th17 cells are believed to be important proinflammatory cells in the pathogenesis of chronic obstructive pulmonary disease (COPD)
A recent study found that IL-17A contributed to cigarette smoke-induced lymphoid neogenesis of late-stage COPD, suggesting that IL-17A is critical in chronic inflammation and adaptive immune responses in COPD [11]
Proportions of T helper 1 (Th1) cells were significantly increased in patients with COPD compared with never-smokers and smokers, and there was a trend for increase in smokers compared with never-smokers (Fig. 1a, Fig. 2a and c)

Summary

Introduction

Th17 cells are believed to be important proinflammatory cells in the pathogenesis of chronic obstructive pulmonary disease (COPD). Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation and an enhanced chronic inflammatory response to noxious particles or gases, cigarette smoke [1, 2]. Evidence shows that chronic inflammation, present in the peripheral and central airways, lung parenchyma and Inflammation in COPD was believed to be driven by T helper 1 (Th1) response, but accumulating evidence supports a critical role of Th17 response in the disease. A recent study found that IL-17A contributed to cigarette smoke-induced lymphoid neogenesis of late-stage COPD, suggesting that IL-17A is critical in chronic inflammation and adaptive immune responses in COPD [11]. IL-17A expression is not sufficient to define the pathogenic activity of Th17 cells, which represent heterogeneous populations with distinct trafficking profiles and abilities to provoke autoimmune diseases [12]

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