Neutrophil and macrophage zonation in liver disease: from spatiotemporal dynamics to advanced computational analysis

Liver disease progression is profoundly shaped by the spatial and temporal dynamics of innate immune cells, particularly neutrophils and macrophages. Recent advances in single-cell and spatial omics, intravital imaging, and multiplexed histology have revealed how these cells exhibit distinct zonation patterns along the portal-central axis and undergo dynamic reprogramming in response to injury, infection, and metabolic stress. Neutrophils preferentially accumulate in necrotic or pericentral zones, whereas macrophage subsets adopt diverse zonal identities and display remarkable plasticity, collectively orchestrating inflammation and tissue repair. In this review, we consolidate current knowledge on neutrophil and macrophage zonation in liver disease, emphasizing their roles in shaping pathophysiology and clinical outcomes. We also briefly outline how emerging technologies are refining our understanding of immune microanatomy and may pave the way for precision hepatology.