Macrophage Modulation In Salivary Glands Secretion And Immunity Under Hypoxia

This study investigates the impact of obstructive sleep apnea (OSA)-related hypoxic stress on the secretion and immunity of salivary glands (SG), with a particular focus on macrophage modulation. We aim to explore the role of macrophages in maintaining SG homeostasis under low-oxygen conditions and identify potential salivary biomarkers for OSA diagnosis. Using a C57BL/6J mouse model of OSA, we exposed mice to varying levels of intermittent hypoxia to simulate OSA conditions. SG function was assessed by measuring salivation rates, mucus secretion, and calcium crystal deposition. The immune cell composition, particularly macrophages, was analyzed using immunohistochemistry, flow cytometry and RNA sequencing. The in vivo macrophage phagocytosis was evaluated through retroductal infusion of fluorescent latex beads. The interaction between salivary epithelial cells and macrophages was examined through in vivo imaging and gene expression analysis. Saliva from OSA patients was collected to validate findings and explore potential biomarkers. OSA-induced hypoxia led to a significant reduction in salivary flow rate and changes in glandular morphology. Macrophages in the ductal regions showed reduced numbers and impaired phagocytic function. Elevated levels of IL-34 and CSF1, key macrophage-related factors, were observed in both mice and human saliva, correlating with the severity of OSA. Hypoxic stress associated with OSA disrupts both salivary secretion and immune surveillance, particularly through macrophage dysfunction. These findings suggest that salivary macrophage-related biomarkers could serve as non-invasive tools for OSA diagnosis and monitoring, providing insights for targeted therapeutic interventions in SG and immune system health.