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Single-cell atlas reveals alveolar macrophage-specific Oncostatin-M drives pulmonary fibrosis via fibroblast activation in PCV2d infection

Xu, J.; Fan, X.; Chen, P.; Yuan, Y.; Chen, Y.; Fan, G.; Yang, B.; Yang, F.; Zhang, S.; Wang, Y.

2025-12-10 genomics
10.64898/2025.12.08.692949 bioRxiv
Show abstract

A hallmark of pulmonary fibrosis is the aberrant activation of lung fibroblasts into pathological fibroblasts that produce excessive extracellular matrix(1). Clarifying the cell-specific mechanisms by which viruses induce this process is crucial for developing effective strategies to intervene in disease progression. Here, we demonstrate that alveolar macrophage subsets specifically express tumor suppressor M (Osm) after infection by PCV2d infection and related intervention experiments in mice, combined with single-cell transcriptome sequencing (scRNA-seq). Through validation using histopathological analyses and an in vitro macrophage-fibroblast co-culture model, these alveolar macrophage-derived oncostatin M (Osm) were confirmed to specifically drive fibroblast activation. Vaccine intervention experiments further confirmed that targeted inhibition of oncostatin M (Osm) expression in alveolar macrophages significantly attenuated fibroblast activation and extracellular matrix deposition, thereby mitigating pulmonary fibrosis progression. Therefore, subgroup-specific secretion of oncostatin M (Osm) by alveolar macrophages represents a key driver mediating PCV2d infection-induced pulmonary fibrosis, and targeting this pathway offers a potential therapeutic strategy for viral-induced pulmonary fibrosis.

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