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

Ulcerative colitis (UC) is a chronic inflammatory bowel disorder with cellular heterogeneity. To understand the composition and spatial changes of the UC ecosystem, we use imaging mass cytometry (IMC) and single-cell RNA sequencing (scRNA-seq) to depict the single-cell landscape of the human colon ecosystem. We find tissue topological changes featured with macrophage disappearance reaction (MDR) in the UC region, occurring only for tissue-resident macrophages. Reactive oxygen species (ROS) levels are higher in the UC region, but ROS scavenging enzyme SOD2 is barely detected in resident macrophages, resulting in distinct ROS vulnerability for inflammatory macrophages and resident macrophages. Inflammatory macrophages replace resident macrophages and cause a spatial shift of TNF-α production during UC via a cytokine production network formed with T and B cells. Our study discovers the mechanism of MDR of resident macrophages, providing novel mechanistic hints for MDR in other inflammation or infection situations. Four healthy control subjects and 4 UC patients were enrolled. 4 pinch biopsy specimens from the healthy volunteers served as healthy control (HC group). For each of the 4 patients, 1 pinch biopsy specimen was collected from the inflamed colon region as the UC group, and 1 pinch biopsy specimen from the normal ascending colon of patients served as self-control (UCSC group).