LAIR-1 limits macrophage activation in acute inflammatory lung injury

Abstract

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are serious health problems that manifest as acute respiratory failure in response to different conditions, including viral respiratory infections. Recently, the inhibitory properties of leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) were demonstrated in allergic and viral airway inflammation. In this study, we investigate the implication of LAIR-1 in ALI/ARDS and explore the underlying mechanisms. Polyinosinic:polycytidylic acid, a synthetic analog of double-stranded RNA, was used to mimic acute inflammation in viral infections. We demonstrate that LAIR-1 is predominantly expressed on macrophages and regulates their recruitment to the lungs as well as their activation in response to polyinosinic:polycytidylic acid. Interestingly, LAIR-1 deficiency increases neutrophil recruitment as well as lung resistance and permeability. In particular, we highlight the capacity of LAIR-1 to regulate the secretion of CXCL10, considered a key marker of macrophage overactivation in acute lung inflammation. We also reveal in COVID-19-induced lung inflammation that LAIR1 is upregulated on lung macrophages in correlation with relevant immune regulatory genes. Altogether, our findings demonstrate the implication of LAIR-1 in the pathogenesis of ALI/ARDS by means of the regulation of macrophages, thereby providing the basis of a novel therapeutic target.