Mass Cytometry and Single-Cell Transcriptome Analyses Reveal the Immune Cell Characteristics of Ulcerative Colitis

Background: The pathogenesis of ulcerative colitis (UC) is closely related to immunity. The immune characteristic differences between active UC (UCa) and inactive UC (UCin) have not been completely explained. Mass cytometry (CyTOF) and single-cell RNA sequencing (scRNA-seq) were used to analyze the immune cells of UCa, UCin and healthy control (HC) subjects to determine the specific immune characteristics. Methods: The immune cell subsets among UCa, UCin, HC were distinguished using CyTOF analysis. scRNA-seq analysis was used to validate the results of CyTOF. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to understand the roles of differential immune cell subsets. Results: After CyTOF analysis and validation of scRNA-seq analysis, differential immune cell subsets mainly contained TNFIL17A effector memory (EM) Tregs, CXCR3CTLA4 EM Tregs, CXCR3CCR7 B cells, HLA-DRCCR7 dendritic cells (DCs) and CTLA-4 natural killer (NK) cells. In comparison to HC, CCR6TNFCD161 EM T cells were highly enriched in UCa and UCin. Besides, UCa was characterized by an increase in CD38TNF EM Tregs, CXCR3CCR4 naïve B cells, HLA-DRCD14IL21 macrophages/monocytes, HLA-DRCCR7 DCs, AHRCD14 cytotoxic NK (cNK) cells and CD8AIFNG cNK cells. Decreases in CD38CD27 plasmablasts, CXCR3CD38 regulatory NK cells, and CXCR3CCR7 tolerant NK cells in UCa were discovered. Conclusions: Novel immune cell subsets which was used to distinguish UCa, UCin and HC were identified. This information might be utilized to distinguish the patients with UCa and UCin.