Sun Bingqing, Lin Jiangtao
Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; China-Japan Friendship Hospital (Institute of Clinical Medical Sciences), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
China-Japan Friendship Hospital (Institute of Clinical Medical Sciences), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Transl Res. 2025 May;279:40-54. doi: 10.1016/j.trsl.2025.04.001. Epub 2025 Apr 10.
Different types of T helper cells play an important role in disease severity and treatment response in patients with asthma. The potassium channel Kv1.3 is a type of potentially therapeutic target in T-cell-mediated inflammatory diseases.
This study aimed to explore the potential of Kv1.3 as a therapeutic target for asthma and to assess the efficacy of the Kv1.3 inhibitor PAP-1 in the treatment of asthma.
Kv1.3 expression on CD4T cells was determined using data from public databases. CD4T cells were isolated from peripheral blood samples obtained from healthy individuals and patients with asthma. The mouse models of OVA-induced asthma and Kv1.3 knockout were established. The underlying mechanism was investigated using mouse splenic CD4T cells and BEAS-2B cells. OVA-induced asthmatic mice were treated with the Kv1.3 selective blocker PAP-1.
Based on public data, we determined the distribution of Kv1.3 on CD4T cells, its up-regulation in asthma, and its correlation with Th17/Treg balance. Upregulation of Kv1.3 in CD4T cells was associated with enhanced activation of these cells and airway inflammation in patients and mice with asthma, accompanied by increased IL-17A levels in alveolar lavage fluid. Conversely, Kv1.3 deficiency significantly attenuated airway inflammation, lowered IL-17A levels in bronchoalveolar lavage fluid, and inhibited airway epithelial-mesenchymal transition in asthmatic mice. Furthermore, treatment with the Kv1.3 selective blocker PAP-1 attenuated inflammation in lung tissues and prevented airway remodeling in OVA-induced asthmatic mice.
Kv1.3 expression on CD4 T cells was correlated with IL-17A-associated airway inflammation and remodeling in asthma, which may be regarded as a potential diagnostic marker and therapeutic target for asthma.
Based on our study, Kv1.3 expression on CD4T cells was correlated with IL-17A-associated airway inflammation and remodeling in asthma, which may be regarded as a potential diagnostic marker and therapeutic target for asthma. The treatment with the Kv1.3 selective blocker PAP-1 attenuated inflammation in lung tissues and prevented airway remodeling in OVA-induced asthmatic mice. Our discoveries offer novel perspectives for a better understanding of IL-17A-associated airway remodeling in asthma. The development of drugs targeting Kv1.3 holds application value for IL-17A-associated asthma.
不同类型的辅助性T细胞在哮喘患者的疾病严重程度和治疗反应中发挥着重要作用。钾通道Kv1.3是T细胞介导的炎症性疾病中一种潜在的治疗靶点。
本研究旨在探讨Kv1.3作为哮喘治疗靶点的潜力，并评估Kv1.3抑制剂PAP-1治疗哮喘的疗效。
利用公共数据库的数据确定CD4T细胞上Kv1.3的表达。从健康个体和哮喘患者的外周血样本中分离CD4T细胞。建立卵清蛋白（OVA）诱导的哮喘小鼠模型和Kv1.3基因敲除小鼠模型。使用小鼠脾CD4T细胞和BEAS-2B细胞研究其潜在机制。用Kv1.3选择性阻滞剂PAP-1治疗OVA诱导的哮喘小鼠。
基于公共数据，我们确定了Kv1.3在CD4T细胞上的分布、其在哮喘中的上调情况及其与Th17/Treg平衡的相关性。CD4T细胞中Kv1.3的上调与哮喘患者和小鼠这些细胞的活化增强及气道炎症相关，同时肺泡灌洗液中白细胞介素-17A（IL-17A）水平升高。相反，Kv1.3缺乏显著减轻气道炎症，降低支气管肺泡灌洗液中IL-17A水平，并抑制哮喘小鼠气道上皮-间质转化。此外，用Kv1.3选择性阻滞剂PAP-1治疗可减轻OVA诱导的哮喘小鼠肺组织炎症并预防气道重塑。
CD4 T细胞上Kv1.3的表达与哮喘中IL-17A相关的气道炎症和重塑相关，这可能被视为哮喘的潜在诊断标志物和治疗靶点。
基于我们的研究，CD4T细胞上Kv1.3的表达与哮喘中IL-17A相关的气道炎症和重塑相关，这可能被视为哮喘的潜在诊断标志物和治疗靶点。用Kv1.3选择性阻滞剂PAP-1治疗可减轻OVA诱导的哮喘小鼠肺组织炎症并预防气道重塑。我们的发现为更好地理解哮喘中IL-17A相关的气道重塑提供了新的视角。开发靶向Kv1.3的药物对IL-17A相关哮喘具有应用价值。
