Single-cell CyTOF profiling reveals alterations in B, T and macrophage subsets during murine hepatic aging

Introduction: Population aging is a global demographic shift closely associated with immune dysregulation, which significantly increases the risk of chronic liver diseases. As a crucial immune and metabolic organ, the liver relies on a complex immune network consisting of innate and adaptive cell subsets to maintain homeostasis and defend against invading pathogens. However, the remodeling mechanism of the hepatic immune landscape with aging remains incompletely understood. Methods: We investigated the changes in hepatic immune cell subsets and related molecular profiles during aging, focusing on the identification and characterization of key immune cell populations and their associated gene expression patterns in aged livers. Results: We identified Igd+ B cells in the hepatic immune compartment, which showed a significant reduction in aged livers. This reduction was accompanied by the enrichment of B cell signal transduction pathways and downregulation of genes related to cell migration and receptor binding. Meanwhile, aged livers exhibited selective expansion of multiple CD4+ T cell subsets (Th1, Th2, Th17, Treg) and an increase in resident-derived pro-inflammatory M1 macrophages, whereas CD8+ T cells, double-negative T cells, and most innate lymphoid cell subsets remained stable. Our study delineated age-associated alterations in hepatic B, T, and macrophage subsets as a characteristic feature of murine hepatic immune aging. Discussion: These findings clarify the characteristics of the hepatic immune landscape during aging, providing a valuable reference for future studies on liver aging and the development of strategies to address age-related liver immune dysregulation.