Department of General and Oncological Pulmonology, Medical University of Lodz, Żeromskiego 113 str., 90-549 Lodz, Poland.
Adv Respir Med. 2024 Oct 18;92(5):429-443. doi: 10.3390/arm92050039.
Studies have shown that eosinophilic COPD (eCOPD) is a distinct phenotype of the disease. It is well established that innate lymphoid cells are involved in the development of eosinophilic inflammation. Interleukin(IL)-25, thymic stromal lymphopoietin (TSLP) and IL-33 are a group of cytokines produced by epithelium in response to danger signals, e.g., cigarette smoke, and potent activators of ILC2s. In the present study, we examined circulating and sputum ILC2 numbers and expression of intracellular IL-5 as well as receptors for TSLP, IL-33 and IL-25 by ILC2s in non-atopic COPD patients with and without (neCOPD) airway eosinophilic inflammation and healthy smokers. In addition, we examined the association between ILC2s and clinical indicators of COPD burden (i.e., symptom intensity and risk of exacerbations). ILC2s were enumerated in peripheral blood and induced sputum by means of flow cytometry. We noted significantly greater numbers of airway IL-5ILC2s and TSLPRILC2s in eCOPD compared with neCOPD ( < 0.05 and < 0.01, respectively) and HSs ( < 0.001 for both). In addition, we showed that IL-5ILC2s, IL-17RBILC2s and ST2ILC2s are significantly increased in the sputum of eCOPD patients compared with HSs. In all COPD patients, sputum ILC2s positively correlated with sputum eosinophil percentage (r = 0.48, = 0.002). We did not find any significant correlations between sputum ILC2s and dyspnea intensity as measured by the modified Medical Research Council scale (mMRC) and symptom intensity measured by the COPD Assessment Test (CAT). These results suggest the involvement of epithelial alarmin-activated ILC2s in the pathobiology of eosinophilic COPD.
研究表明，嗜酸性 COPD（eCOPD）是该疾病的一种独特表型。先天淋巴样细胞（ILC）参与嗜酸性炎症的发展已得到证实。白细胞介素（IL）-25、胸腺基质淋 巴生成素（TSLP）和 IL-33 是一组上皮细胞在受到危险信号（例如香烟烟雾）刺激时产生的细胞因子，是 ILC2 的有力激活剂。在本研究中，我们检查了非特应性 COPD 患者（伴或不伴气道嗜酸性炎症）和健康吸烟者外周血和痰中 ILC2 数量以及细胞内 IL-5 和 TSLP、IL-33 和 IL-25 受体的表达。此外，我们还检查了 ILC2 与 COPD 负担的临床指标（即症状严重程度和恶化风险）之间的关联。通过流式细胞术在外周血和诱导痰中计数 ILC2。我们注意到，与 neCOPD（分别为 < 0.05 和 < 0.01）和 HS（均 < 0.001）相比，eCOPD 患者气道中 IL-5ILC2 和 TSLPRILC2 的数量明显更多。此外，我们还表明，与 HS 相比，eCOPD 患者的痰中 IL-5ILC2、IL-17RBILC2 和 ST2ILC2 的数量显著增加。在所有 COPD 患者中，痰 ILC2 与痰嗜酸性粒细胞百分比呈正相关（r = 0.48， = 0.002）。我们没有发现痰 ILC2 与改良医学研究理事会量表（mMRC）衡量的呼吸困难严重程度和 COPD 评估测试（CAT）衡量的症状严重程度之间存在任何显著相关性。这些结果表明上皮警报素激活的 ILC2 参与了嗜酸性 COPD 的发病机制。
