Work

Dynamics of severity-associated immune remodeling by granulocytes and macrophages in acute lung injury

Year: 2026

Type: article

Abstract: Acute lung injury (ALI) is driven by dysregulated alveolar immune responses. While granulocytes and macrophages are critical effectors, their coordinated molecular reprogramming and severity-associated crosstalk shape immune remodeling during disease progression. Here, we performed single-cell RNA sequencing (scRNA-seq) of bronchoalveolar lavage fluid from patients with intermediate- and late-severity ALI to map immune microenvironment remodeling. We observed pronounced granulocyte expansion coupled with macrophage depletion. Granulocytes exhibit distinct transcriptional states along a continuum from acute migratory states toward pro-inflammatory, metabolically reprogrammed subsets, dominated by TNF and MAPK signaling. Simultaneously, macrophages shift toward inflammatory M1-like phenotypes, characterized by distinct metabolic reprogramming and reduced oxidative phosphorylation. Furthermore, we infer a granulocyte-centric inflammatory network mediated through TNF, IFN, and RESISTIN pathways, suggesting a feedforward inflammatory loop. Collectively, this study elucidates the transcriptional and metabolic reprogramming associated with escalating ALI severity, providing a framework for severity-adapted therapeutic interventions to restore pulmonary homeostasis.

Source: iScience

DOI: 10.1016/j.isci.2026.115816