Siglec-F exerts protective effects on elastase-induced lung inflammation and emphysema in mice 2288

Description Airspace macrophages (AMs) are crucial for host defense, but protection must occur with minimal physiological disruption. Indeed, activated AMs release proteases that cause alveolar destruction in patients with emphysema. Siglecs are inhibitory immunoreceptors that prevent activation of leukocytes, including AMs. In health, murine resident AMs (RAMs) express Siglec-F, but its precise function is unknown. We used Siglecf-/- (KO) mice to test its role at baseline and in a model of emphysema caused by porcine pancreatic elastase (PPE) administration to the lungs. We assessed lung inflammation and emphysema using samples obtained 1, 3, 7, and 21 d post-PPE. RAMs were the predominant immune cell type and the main source of Siglec-F expression. We also identified a subset of neutrophils 1-3 d post-PPE that were Siglec-F+. However, emphysema occurred after neutrophilia resolved (7-21 d post-PPE). KO mice had increased RAMs and worsened emphysema, and bulk RNA-seq revealed that Siglec-F-deficiency altered RAM transcriptional profiles, including pathways associated with inflammation and lipid metabolism. These studies demonstrate that Siglec-F suppresses deleterious effects of RAM activation in the lungs. Further studies focus on Siglec-F-mediated signaling in AMs and how Siglec-F controls pro-emphysema mediators normally suppressed in RAMs. Funding Sources NIH R01HL130938 Topic Categories Mucosal and Regional Immunology (MUC)