The role of macrophages in asthma-related fibrosis and remodelling.

Abstract

Airway remodelling significantly contributes to the progressive loss of lung function and heightened symptom severity in chronic asthma. Additionally, it often persists and demonstrates reduced responsiveness to the mainstay treatments. The excessive deposition of collagen and extracellular matrix proteins leads to subepithelial fibrosis and airway remodelling, resulting in increased stiffness and decreased elasticity in the airway. Studies have emphasized the crucial role of subepithelial fibrosis in the pathogenesis of asthma. Fibrotic processes eventually cause airway narrowing, reduced lung function, and exacerbation of asthma symptoms. Macrophages play a crucial role in this process by producing pro-fibrotic cytokines, growth factors, and enzymes such as matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). Additionally, identification of novel genetic markers has provided evidence for a strong genetic component in fibrosis within macrophage regulated fibrosis. Although macrophages contribute to the progression of airway remodelling and subepithelial fibrosis, interventions targeting macrophage-driven fibrotic changes have not yet been developed. This review synthesizes research on the intricate pathways through which macrophages contribute to subepithelial fibrosis in chronic asthma and its' pathological features. Understanding the interplay between macrophages, fibrosis, and asthma pathogenesis is essential for developing effective therapeutic strategies to manage severe asthma and improve patient outcomes.