Th2 lymphocyte potassium channels in asthma

Abstract

Asthma is characterized by episodes of breathlessness and airway hyper reactivity, often when provoked by allergens. T‐helper type 2 (Th2) lymphocytes are the predominant T cell population in the lungs of patients with asthma and have been linked to asthma pathogenesis. These Th2 cells represent an attractive target for the treatment of asthma. The use of immunomodulators selective for disease‐relevant T cells that do not affect the bulk of the lymphoid compartment would reduce the risk of side effects. We propose Kv1.3 potassium channel blockers for the preferential targeting of lung‐infiltrating Th2 cells. T lymphocytes express two types of potassium channels, Kv1.3 and KCa3.1 during Th1‐mediated chronic inflammatory diseases. We have used whole‐cell patch clamp to show that Th2 cells isolated from induced sputum of patients with asthma up‐regulate Kv1.3 channels upon activation. In contrast, T cells isolated from induced sputum of healthy controls remained Kv1.3low upon activation. In functional assays, we found that T cells stimulated with an allergen are sensitive to a selective Kv1.3 channel blocker. Selective Kv1.3 channel blockers represent attractive targets for the treatment of allergic asthma.This study is funded by an R56 AI084981‐01A1 from NIH/NIAID to Christine Beeton.