Department of Respiratory and Critical Care Medicine, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan, People's Republic of China.
Department of Immune Allergy, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan, People's Republic of China.
Int J Chron Obstruct Pulmon Dis. 2023 Sep 12;18:2027-2038. doi: 10.2147/COPD.S426215. eCollection 2023.
Dysregulation and pyroptosis of T-helper (Th) cells and inflammatory cytokines have been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the immune response mechanisms as a consequence of tobacco smoke exposure are not fully understood. We hypothesized that cigarette smoke-induced inflammation could be modulated through the cytokine milieu and T-cell nicotinic acetylcholine receptors (nAChRs).
The proportions of peripheral blood Th1 and Th2 cells from patients with COPD, smokers without airway obstruction and healthy nonsmokers were analyzed using flow cytometry. The levels of plasma proinflammatory cytokines and their potential association with pulmonary function were also measured. The influence of cigarette smoke extract (CSE) on the conditioned differentiation of T helper cell subsets was further examined in vitro.
Significantly higher Th1 cell and plasma IFN-γ and IL-18 levels but lower levels of Th2 cells were found in the peripheral blood from patients with COPD. The increased plasma levels of IFN-γ and IL-18 were negatively correlated with pulmonary function (FEV1% predicted value). Pyroptosis participates in COPD development probably through the activation of the NLRP3 inflammasome upon exposure to CSE. CSE does not directly induce the differentiation of T helper cells; however, under conditioned medium, CSE promotes Th1 development through α7 nAChR modification, while it does not substantially interfere with Th2 differentiation.
The differences in the cytokine milieu play a key role in the effects of CSE on the immune response in patients with COPD.
T 辅助细胞（Th）功能失调和细胞焦亡以及炎症细胞因子与慢性阻塞性肺疾病（COPD）的发病机制有关。然而，由于吸烟而导致的免疫反应机制尚不完全清楚。我们假设香烟烟雾引起的炎症可以通过细胞因子环境和 T 细胞烟碱型乙酰胆碱受体（nAChRs）来调节。
使用流式细胞术分析 COPD 患者、无气道阻塞的吸烟者和健康不吸烟者的外周血 Th1 和 Th2 细胞的比例。还测量了血浆前炎症细胞因子的水平及其与肺功能的潜在关联。进一步在体外检查香烟烟雾提取物（CSE）对 T 辅助细胞亚群条件分化的影响。
COPD 患者外周血中 Th1 细胞和血浆 IFN-γ和 IL-18 水平明显升高，Th2 细胞水平降低。血浆中 IFN-γ和 IL-18 水平升高与肺功能（FEV1%预测值）呈负相关。焦亡可能通过 NLRP3 炎性体在暴露于 CSE 时的激活参与 COPD 的发展。CSE 不会直接诱导 T 辅助细胞分化；然而，在条件培养基下，CSE 通过 α7 nAChR 修饰促进 Th1 发育，而不会对 Th2 分化产生实质性干扰。
细胞因子环境的差异在 CSE 对 COPD 患者免疫反应的影响中起关键作用。
