Journal Article

Single-cell and spatial multi-omics highlight effects of anti-integrin therapy across cellular compartments in ulcerative colitis

Combes, Alexis J., Lewin, Sara, Dorman, Leah C., Lotstein, Madison L., Patel, Ravi K., Terdiman, Jonathan P., Li, Stephanie, Eckalbar, Walter, Shen, Alan, Rao, Arjun, Fragiadakis, Gabriela K., Mennillo, Elvira, Bain, Jared L., Kattah, Michael G., Flynn, Emily, Cho, Soo-jin, Andersen, Christopher, Bernard-Vazquez, Faviola, Beck, Kendall, Kim, Yang Joon, Oh, David Y., Tsui, Jessica, El-Nachef, Najwa, Lee, Gyehyun, Naser, Mohammad, Selvig, Daniel R., Mahadevan, Uma, Pisco, Angela, Rusu, Iulia, Tamaki, Stanley, Rahim, Maha

2024

Overview

Ulcerative colitis (UC) is driven by immune and stromal subsets, culminating in epithelial injury. Vedolizumab (VDZ) is an anti-integrin 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 perform single-cell transcriptomic and proteomic analyses of peripheral blood and colonic biopsies in healthy controls and patients with UC on VDZ or other therapies. Here we show that VDZ treatment is associated with alterations in circulating and tissue mononuclear phagocyte (MNP) subsets, along with modest shifts in lymphocytes. Spatial multi-omics of formalin-fixed biopsies demonstrates trends towards increased abundance and proximity of MNP and fibroblast subsets in active colitis. Spatial transcriptomics of archived specimens pre-treatment identifies epithelial-, MNP-, and fibroblast-enriched genes related to VDZ responsiveness, highlighting important roles for these subsets in UC. Anti-integrin therapy inhibits lymphocyte trafficking in ulcerative colitis. Here Mennillo et al. use single-cell and spatial -omics to show modulation of mononuclear phagocytes and other networks, identifying gene sets related to treatment response.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13/31 / 38/91 / 631/250/347 / 631/553/1833 / 631/80/304 / 692/53/2421 / Antibodies / Biopsy / Colitis, Ulcerative - drug therapy / Colitis, Ulcerative - genetics / Fibroblasts / Gastrointestinal Agents - therapeutic use / Humanities and Social Sciences / Humans / Inflammatory bowel disease / Inflammatory bowel diseases / Integrins - genetics / Intestine / Leukocytes (mononuclear) / Lymphocytes / Monoclonal antibodies / multidisciplinary / Multiomics / Peripheral blood / Phagocytes / Proteomics / Retrospective Studies / Science / Science (multidisciplinary) / Transcriptomics / Treatment Outcome / Ulcerative colitis