Eosinophil-derived interleukin-24 compromises epithelial integrity and aggravates airway remodeling in mouse models of allergic asthma.

Abstract

Asthma is a heterogeneous disease characterized by infiltration of immune cells that interact with epithelial cells and release various factors driving chronic inflammation and airway remodeling. Although monoclonal antibody-based biologics alleviate inflammation, their efficacy in suppressing airway remodeling is limited. Interleukin-24 (IL-24) has been implicated in neutrophilic asthma, but its role in eosinophilic asthma remains unclear. Here, we show that IL-24 is mainly secreted by infiltrating eosinophils in mice with OVA- and HDM-induced asthma-like lung disease models. IL-24 knockout mice exhibit reduced inflammatory responses, alleviated pulmonary fibrosis, improved epithelial integrity, and decreased mucus hypersecretion. Mechanistically, IL-24 activates the CXCL5/CXCR1/CXCR2 axis, enhancing eosinophil recruitment to the lungs. IL-24 disrupts epithelial tight junction integrity, contributing to increased permeability. Furthermore, IL-24 targets airway epithelial cells, promoting EMT-like changes and the secretion of profibrotic mediators, which leads to bronchial wall thickening and pulmonary fibrosis. Therefore, targeting IL-24 holds promise for anti-asthmatic interventions by suppressing inflammation and pathological remodeling.