Identification of a subset of lung neutrophils that promote Acute Lung Injury resolution in mice

Abstract The acute respiratory distress syndrome (ARDS) is a major cause of failure with limited therapeutic options. Unresolving inflammation in the lungs and alveolar-capillary barrier dysfunction are main features ARDS. sharp increase incidence ARDS during COVID19 emphasized need for better understanding immunological events that inform novel therapeutics. Here, we used model self-limited acid-induced ALI by selectively instilling HCL to left lung adult mice. time-course was determined via quantification consolidation micro-computed tomography, while assessed histology flow cytometry. Neutrophils, rapidly recruited into lungs, decreased over time resolution macrophage numbers, reduced initial stages, increased. Immunophenotyping leukocyte recruitment injury uncovered neutrophils’ subset expressing SiglecF. These cells were distinct from eosinophils phenotypically, functionally different classical SiglecF-negative neutrophils. roles SiglecF+ neutrophils further vitro functional studies, adoptive transfer experiments, lipidomic analysis. Depletion impaired alveolar epithelial cell type II (AT2) repair, accelerated restitution. Among mechanisms associated repair production specialized pro-resolving mediators CSF1. In sum, identified protective tissue