Nature Communications (Feb 2024)
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,
- Michael G. Kattah
Affiliations
- Elvira Mennillo
- Department of Medicine, University of California San Francisco
- Yang Joon Kim
- Chan Zuckerberg Biohub
- Gyehyun Lee
- Department of Medicine, University of California San Francisco
- Iulia Rusu
- Department of Medicine, University of California San Francisco
- Ravi K. Patel
- Department of Medicine, University of California San Francisco
- Leah C. Dorman
- Chan Zuckerberg Biohub
- Emily Flynn
- CoLabs, University of California San Francisco
- Stephanie Li
- Department of Medicine, University of California San Francisco
- Jared L. Bain
- Department of Medicine, University of California San Francisco
- Christopher Andersen
- Department of Medicine, University of California San Francisco
- Arjun Rao
- Department of Medicine, University of California San Francisco
- Stanley Tamaki
- CoLabs, University of California San Francisco
- Jessica Tsui
- Department of Medicine, University of California San Francisco
- Alan Shen
- Department of Medicine, University of California San Francisco
- Madison L. Lotstein
- Department of Medicine, University of California San Francisco
- Maha Rahim
- Helen Diller Family Comprehensive Cancer Center, University of California San Francisco
- Mohammad Naser
- Biological Imaging Development CoLab, University of California San Francisco
- Faviola Bernard-Vazquez
- Department of Medicine, University of California San Francisco
- Walter Eckalbar
- CoLabs, University of California San Francisco
- Soo-jin Cho
- Department of Pathology, University of California San Francisco
- Kendall Beck
- Department of Medicine, University of California San Francisco
- Najwa El-Nachef
- Department of Medicine, University of California San Francisco
- Sara Lewin
- Department of Medicine, University of California San Francisco
- Daniel R. Selvig
- Department of Medicine, University of California San Francisco
- Jonathan P. Terdiman
- Department of Medicine, University of California San Francisco
- Uma Mahadevan
- Department of Medicine, University of California San Francisco
- David Y. Oh
- Department of Medicine, University of California San Francisco
- Gabriela K. Fragiadakis
- Department of Medicine, University of California San Francisco
- Angela Pisco
- Chan Zuckerberg Biohub
- Alexis J. Combes
- Department of Medicine, University of California San Francisco
- Michael G. Kattah
- Department of Medicine, University of California San Francisco
- DOI
- https://doi.org/10.1038/s41467-024-45665-6
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 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.
