Fibroblast-centered mechanisms of chronic inflammation and airway remodeling in allergic bronchopulmonary aspergillosis.

Allergic bronchopulmonary aspergillosis (ABPA) is a complex hypersensitivity lung disease driven predominantly by type 2 immune responses. However, the classical immunological paradigm fails to adequately explain the persistent airway structural damage and frequent relapses observed even after inflammatory control is achieved. This review proposes a fibroblast-centered mechanistic framework that synthesizes evidence from ABPA, fungal-associated airway diseases, and pulmonary fibrosis to systematically delineate the mechanisms linking fibroblasts to chronic inflammation and airway remodeling. In the context of chronic inflammation and persistent epithelial injury, fibroblasts can be activated by various signals, including type 2 cytokines such as interleukin-4 (IL-4) and IL-13. Upon activation, fibroblasts exert their effects through functionally distinct subpopulations: they actively recruit eosinophils through chemokine secretion (e.g., CCL11), establishing a positive feedback loop of "epithelial injury-fibroblast activation-eosinophil infiltration-tissue damage" that sustains and amplifies inflammation. Prolonged activation further drives fibroblast-to-myofibroblast transition, characterized by expression of α-smooth muscle actin (α-SMA) and deposition of excessive extracellular matrix, resulting in irreversible airway remodeling and central bronchiectasis. Clinically, fibroblast-related markers such as periostin, transforming growth factor-β, and α-SMA show promise for future risk stratification. Biologics targeting fibrotic pathways have already demonstrated anti-remodeling potential. In the future, the integration of single-cell transcriptomics, spatial omics, and longitudinal clinical studies may clarify the roles of distinct fibroblast subpopulations in ABPA progression and treatment response. This integration could also enable the establishment of a comprehensive "inflammation-remodeling" assessment system-facilitating a therapeutic transition from pure immunosuppression toward combined modulation of tissue repair.