Divergent spatial microdomains drive inflammation and repair in Ulcerative and Immune Checkpoint Therapy Colitis - Spatial Transcriptomics

Adult inflammatory bowel disease is incompletely understood. We combine unbiased single-cell RNA sequencing (gene expression profiling, CITE-seq derived cell surface protein data, TCR and BCR sequence data) with unbiased spatial transcriptomics to interrogate changes across immune and non-immune populations in colitis and health, across tissue and blood. We compare idiopathic ulcerative colitis with hitherto under-studied immune checkpoint therapy induced colitis, utilizing non-inflamed disease states as additional controls. We identify patterns of inflammation and response unique and common to both diseases, and infer changes in cell trafficking with potential therapeutic implications. We go on to localize disease-specific changes in tissue using spatial transcriptomics, leveraging this data to interrogate cellular interactions in an unbiased manner, allowing us to describe novel microdomains of inflammation and repair. Overall design: Colon sections from adult healthy patients (HC) and adults with actively inflamed ulcerative colitis (UC_I) and checkpoint inhibitor-induced colitis (CC_I) were subject to unbiased spatial transcriptomic analysis using the 10X visium platform. Patients with CC were either treated with anti-PD-1 immunotherapy (Monotherapy) or a combination of simultaneous anti-PD-1 and anti-CTLA4 immunotherapy (Dual therapy).