# IL-1β+ lung-resident macrophages mediate endothelial dysfunction and acute lung injury in sepsis through immune-metabolic crosstalk

## TL;DR

This study shows that IL-1β-producing lung macrophages worsen lung injury in sepsis by disrupting blood vessel function and altering metabolism.

## Contribution

The paper identifies a novel immune-metabolic crosstalk mechanism involving IL-1β+ macrophages in sepsis-induced lung injury.

## Key findings

- IL-1β+ macrophages promote endothelial dysfunction and vascular leakage in sepsis.
- Metabolomics and co-culture experiments reveal IL-1β impairs endothelial integrity and metabolism.
- Targeting IL-1β may offer therapeutic benefits for acute lung injury in sepsis.

## Abstract

Sepsis-induced acute lung injury (ALI) involves a complex interplay between immune cells and the pulmonary endothelium. However, the molecular regulators that coordinate this interaction remain poorly defined. In a murine sepsis model, we identified a subset of lung-resident macrophages characterized by robust IL-1β expression as pivotal contributors to lung damage. Single-cell RNA sequencing (scRNA-seq) delineated a distinct IL-1β⁺ macrophage population with pronounced pro-inflammatory transcriptional features and enhanced endothelial communication. These macrophages exhibited intensified ligand–receptor interactions with pulmonary endothelial cells, corresponding with elevated vascular leakage and histopathological evidence of injury. Immunoassays, Western blotting, and histopathology confirmed IL-1β upregulation during lung injury. Furthermore, metabolomics and in vitro co-culture experiments demonstrated that IL-1β impairs endothelial integrity and modulates metabolic activity. This study reveals a novel immune-metabolic axis whereby IL-1β+ macrophages orchestrate endothelial dysfunction and tissue injury in sepsis. Our findings highlight IL-1β as a potential therapeutic target for mitigating ALI in septic patients.