Extracellular matrix anchored neutrophils drive pulmonary fibrosis in mice.

ABSTRACT: Pulmonary fibrosis (PF) is a progressive lung disease characterized by chronic immune dysregulation and excessive extracellular matrix (ECM) remodeling. Neutrophils, traditionally linked to acute inflammation, are increasingly recognized for their role in fibrosis. In this study, we identified a unique subset of neutrophils undergoing reverse transendothelial migration (rTEM) in the lungs of a silicosis mouse model induced by intratracheal SiO₂ instillation. Using single-cell RNA sequencing (scRNA-seq), spatial transcriptomics (ST), and ECM proteomics, we found that rTEM neutrophils were retained in fibrotic regions via ICAM1-mediated interactions with the ECM. Mechanistically, macrophage-derived cathepsin C (CTSC), accumulating in the ECM, cleaved ICAM1 into its soluble form (sICAM1), whi

SUBMITTER: Yang L 

PROVIDER: S-EPMC12749320 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature