Single-cell and spatial multi-omics highlight effects of anti-integrin therapy across cellular compartments in ulcerative colitis [biopsy scRNA-seq]

Ulcerative colitis (UC) is a chronic inflammatory condition of the colon, driven by mucosal immune and stromal subsets, culminating in epithelial injury. Vedolizumab (VDZ) is an anti-integrin monoclonal antibody that is effective for treating UC. VDZ is known to inhibit lymphocyte trafficking to the intestine, but its broader effects on other cell subsets are less defined. To identify the inflammatory cells that contribute to colitis and are affected by VDZ, we performed a single-cell and spatial transcriptomic and proteomic analysis of peripheral blood and colonic biopsies in healthy controls (HC) and patients with UC on VDZ or other therapies. We identified significant effects of VDZ on mononuclear phagocyte (MNP) subsets, in addition to modest effects on lymphocyte populations. Spatial transcriptomics and proteomics of formalin-fixed, paraffin-embedded (FFPE) biopsies at single-cell resolution demonstrated trends towards increased abundance and proximity of activated MNP and fibroblast subsets in active colitis compared to HC, with inhibition by VDZ. Spatial transcriptomics of archived FFPE specimens pre-treatment identified epithelial-, MNP-, and fibroblast-enriched genes related to VDZ response versus non-response, and these were validated in an external, publicly accessible bulk transcriptomic dataset. Single cell and spatial multi-omics highlight important roles for myeloid, stromal, and epithelial subsets in UC.