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

Ulcerative colitis is a chronic inflammatory bowel disorder with cellular heterogeneity. To understand the composition and spatial changes of the ulcerative colitis ecosystem, here we use imaging mass cytometry and single-cell RNA sequencing to depict the single-cell landscape of the human colon ecosystem. We find tissue topological changes featured with macrophage disappearance reaction in the ulcerative colitis region, occurring only for tissue-resident macrophages. Reactive oxygen species levels are higher in the ulcerative colitis region, but reactive oxygen species scavenging enzyme SOD2 is barely detected in resident macrophages, resulting in distinct reactive oxygen species vulnerability for inflammatory macrophages and resident macrophages. Inflammatory macrophages replace resident macrophages and cause a spatial shift of TNF production during ulcerative colitis via a cytokine production network formed with T and B cells. Our study suggests components of a mechanism for the observed macrophage disappearance reaction of resident macrophages, providing mechanistic hints for macrophage disappearance reaction in other inflammation or infection situations. Ulcerative colitis is associated with increased infiltration and cellularity, yet the precise tissue topology remains poorly understood. Here the authors employ imaging mass cytometry and single-cell RNA sequencing to characterise intestinal lesions in patients with ulcerative colitis, and show the architecture at the individual cell level which includes a decrease in the resident macrophage population.

Automated summary

By using imaging mass cytometry and single-cell RNA sequencing, researchers characterized the single-cell landscape of the human colon ecosystem in ulcerative colitis. They found tissue topological changes and a disappearance reaction of tissue-resident macrophages in the ulcerative colitis region. The study also revealed different reactive oxygen species vulnerability between inflammatory macrophages and resident macrophages, as well as a cytokine production network formed with T and B cells.