Selective oxidative protection leads to tissue topological changes orchestrated by macrophage during ulcerative colitis

Abstract Background and Aims: Ulcerative colitis(UC) is a chronic inflammatory bowel disorder with highly cellular heterogeneity. Mass cytometry(Cy-TOF) and single-cell RNA sequencing (scRNA-seq) have revealed cellular heterogeneity of UC. However, comprehensive elucidation of tissue topological changes within the UC ecosystem is still missing. And we aimed to illustrate compositional and spatial changes of the UC ecosystem.Methods: Imaging mass cytometry (IMC) and scRNA-seq were applied to depict the single-cell landscape of colon ecosystem.Results: We noticed tissue topological changes featured with macrophage disappearance reaction (MDR) in UC region. MDR only occurred for CD163+ tissue-resident macrophages. We found reactive oxygen species (ROS) level were higher in UC region but ROS scavenging enzyme SOD1/2 were barely detected in resident macrophages, resulting selective oxidative protection for inflammatory macrophages and resident macrophage disappearance reaction. Furthermore, inflammatory macrophages replaced resident macrophages during UC, which played a key role in forming the inflammatory cellular network by producing TNF-α and IL-1β. Conclusions: Our study dissected the microenvironment of UC lesions at single-cell resolution while preserving its architecture, based on which, we discovered the mechanism of MDR in UC region and resident macrophage specific MDR resulted in infiltration of inflammatory macrophage, which formed the cytokine producing network within the local cellular neighborhood.