Kv1.3 expression on CD4 (+) T cells promotes interleukin-17A-associated airway inflammation and airway remodeling in asthma.

Background: 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.

Objective: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Translational Significance: 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.