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

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

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: Abstract 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.

Date: 2024
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DOI: 10.1038/s41467-024-45665-6

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