CXCR4 and silicosis: To further delineate macrophage heterogeneity and functional specialisation during silicosis progression, we focused on key macrophage subpopulations.<h4>Results</h4>AMD3100 dynamically remodels the alveolar macrophages (AMs) niche, promoting the restoration of AM homeostasis and significantly reducing both co-expression and spatial co-localisation of Cxcr4/transforming growth factor-β (TGF-β) signalling within macrophages, thereby modulating the fibrotic immune microenvironment.