Th17 and Tc17 cells may be involved in the pathogenesis of chronic obstructive pulmonary disease (COPD), a disease caused predominantly by cigarette smoking. Smoking cessation is the only intervention in the management of COPD. However, even after cessation, the airway inflammation may be present. In the current study, mice were exposed to room air or cigarette smoke for 24 weeks or 24 weeks followed by 12 weeks of cessation. Morphological changes were evaluated by mean linear intercepts (Lm) and destructive index (DI). The frequencies of CD8+IL-17+(Tc17) and CD4+IL-17+(Th17) cells, the mRNA levels of ROR gamma and IL-17, and the levels of IL-8, TNF-alpha, and IFN-gamma in lungs or bronchoalveolar lavage fluid of mice were assayed. Here we demonstrated that alveolar enlargement and destruction induced by cigarette smoke exposure were irreversible and that cigarette smokeenhanced these T-cell subsets, and related cytokines were not significantly reduced after smoking cessation. In addition, the frequencies of Th17 and Tc17 cells in lungs of smoke-exposed mice and cessation mice were positively correlated with emphysematous lesions. More important, the frequencies of Tc17 cells were much higher than Th17 cells, and there was a significantly positive correlation between Th17 and Tc17. These results suggested that Th17/Tc17 infiltration in lungs may play a critical role in sustaining lung inflammation in emphysema. Blocking the abnormally increased numbers of Tc17 and Th17 cells may be a reasonable therapeutic strategy for emphysema. 1. Introduction Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation due to airway obstruction and emphysematous destruction [1]. Smoking is the most important etiological factor in the development of airway inflammation in COPD [1]. Until now, smoking cessation is regarded as the most important intervention in reducing the progression of COPD [2]. However, in those who develop COPD this inflammatory response persists after smoking cessation, suggesting an abnormal regulation mechanism similar to those occurring in autoimmune disorders. COPD shares some features with autoimmune diseases [3–5]. Th1/Tc1 cells contribute principally, but not exclusively, to the pathogenesis of COPD. Th17 cells are now defined as a separate T-cell subset distinct from the Th1 and Th2 cells, with the expression of distinctive transcription factor ROR-ct (RAR-related orphan nuclear receptor ct in mice; RORC, RAR-related orphan nuclear receptor C in humans). IL-17A, IL-17F, IL-21, and IL-22 are secreted by and
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