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An esophagus cell atlas reveals dynamic rewiring during active eosinophilic esophagitis and remission

Author

Listed:
  • Jiarui Ding

    (Broad Institute of MIT and Harvard
    University of British Columbia)

  • John J. Garber

    (Massachusetts General Hospital
    Harvard Medical School)

  • Amiko Uchida

    (Massachusetts General Hospital)

  • Ariel Lefkovith

    (Broad Institute of MIT and Harvard)

  • Grace T. Carter

    (Broad Institute of MIT and Harvard)

  • Praveen Vimalathas

    (Massachusetts General Hospital
    Harvard Medical School)

  • Lauren Canha

    (Massachusetts General Hospital)

  • Michael Dougan

    (Massachusetts General Hospital)

  • Kyle Staller

    (Massachusetts General Hospital)

  • Joseph Yarze

    (Massachusetts General Hospital)

  • Toni M. Delorey

    (Broad Institute of MIT and Harvard)

  • Orit Rozenblatt-Rosen

    (Broad Institute of MIT and Harvard
    Genentech)

  • Orr Ashenberg

    (Broad Institute of MIT and Harvard)

  • Daniel B. Graham

    (Broad Institute of MIT and Harvard
    Harvard Medical School
    Harvard Medical School
    Harvard Medical School)

  • Jacques Deguine

    (Broad Institute of MIT and Harvard)

  • Aviv Regev

    (Broad Institute of MIT and Harvard
    Massachusetts Institute of Technology
    Genentech)

  • Ramnik J. Xavier

    (Broad Institute of MIT and Harvard
    Harvard Medical School
    Harvard Medical School
    Harvard Medical School)

Abstract

Coordinated cell interactions within the esophagus maintain homeostasis, and disruption can lead to eosinophilic esophagitis (EoE), a chronic inflammatory disease with poorly understood pathogenesis. We profile 421,312 individual cells from the esophageal mucosa of 7 healthy and 15 EoE participants, revealing 60 cell subsets and functional alterations in cell states, compositions, and interactions that highlight previously unclear features of EoE. Active disease displays enrichment of ALOX15+ macrophages, PRDM16+ dendritic cells expressing the EoE risk gene ATP10A, and cycling mast cells, with concomitant reduction of TH17 cells. Ligand–receptor expression uncovers eosinophil recruitment programs, increased fibroblast interactions in disease, and IL-9+IL-4+IL-13+ TH2 and endothelial cells as potential mast cell interactors. Resolution of inflammation-associated signatures includes mast and CD4+ TRM cell contraction and cell type-specific downregulation of eosinophil chemoattractant, growth, and survival factors. These cellular alterations in EoE and remission advance our understanding of eosinophilic inflammation and opportunities for therapeutic intervention.

Suggested Citation

  • Jiarui Ding & John J. Garber & Amiko Uchida & Ariel Lefkovith & Grace T. Carter & Praveen Vimalathas & Lauren Canha & Michael Dougan & Kyle Staller & Joseph Yarze & Toni M. Delorey & Orit Rozenblatt-R, 2024. "An esophagus cell atlas reveals dynamic rewiring during active eosinophilic esophagitis and remission," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47647-0
    DOI: 10.1038/s41467-024-47647-0
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    References listed on IDEAS

    as
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