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

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-Rosen, Orr Ashenberg, Daniel B. Graham, Jacques Deguine, Aviv Regev () and Ramnik J. Xavier ()
Additional contact information
Jiarui Ding: Broad Institute of MIT and Harvard
John J. Garber: Massachusetts General Hospital
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
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
Orr Ashenberg: Broad Institute of MIT and Harvard
Daniel B. Graham: Broad Institute of MIT and Harvard
Jacques Deguine: Broad Institute of MIT and Harvard
Aviv Regev: Broad Institute of MIT and Harvard
Ramnik J. Xavier: Broad Institute of MIT and Harvard

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: 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.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-47647-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47647-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-47647-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().