Background: Eosinophils, the major effector cells involved in the pathogenesis of allergic inflammatory diseases, have been reported to have lysosome-associated features. However, information on the role of lysosome in eosinophil functions and asthma is not available.

Objectives: To study the lysosome in eosinophil activation and the pathogenesis of allergic airway inflammation.

Methods: Lysosome-associated gene expression were analyzed in eosinophil activation by RNA-seq. LysoTracker, Lysosome-associated membrane proteins and cathepsins were detected in eosinophil activation. The effects of lysosomal acid inhibitor and cathepsin inhibitors on eosinophil activation in vitro and on allergic airway inflammation in vivo were explored.

Results: The results of RNA-seq suggested vacuolar ATPases and cathepsins were highly expressed in activated eosinophils. Increased LysoTracker and activated cathepsins in eosinophils were found in allergic airway inflammation in vivo and activated eosinophils in vitro. Administration of lysosomal acid inhibitor and cathepsin inhibitors significantly inhibited the expression and secretion of inflammatory cytokines in eosinophils in vitro. Cathepsin inhibitors also attenuated allergic airway inflammation in vivo.

Conclusions: Lysosomes may play an important role in the pathogenesis of allergic airway inflammation by mediating the activation of eosinophils.