ScRNA-seq of Neutrophils upon acute lung injury in a biomaterial-induced chronic inflammatory mouse model

This study investigates the mechanism underlying increased morbidity in individuals with chronic inflammatory conditions upon a secondary inflammatory challenge. Using mouse models, we identified a pronounced expansion of circulating immature neutrophils during chronic inflammation via single-cell RNA sequencing. Functional assays revealed these neutrophils are dysregulated. We established their causal role in exacerbating immunopathology and demonstrated that therapeutic intervention with antibodies or small molecules to block their migration or function significantly reduces tissue damage. This work defines a pathological cell population and proposes a novel therapeutic strategy for patients with chronic inflammatory diseases.