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

• DOI: 10.1038/s41467-024-47647-0
• Publication Date: 2024-04-18T14:01:57Z
• Authors: 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...; Orr Ashenberg; Daniel B. Graham; Jacques Deguine; Aviv Regev; Ramnik J. Xavier
• Keywords: Eosinophilic Esophagitis; Pathogenesis; Interleukin 13

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 esophageal mucosa of 7 healthy 15 EoE participants, revealing 60 subsets functional alterations in states, compositions, that highlight previously unclear features EoE. Active displays enrichment ALOX15 + macrophages, PRDM16 dendritic expressing risk gene ATP10A , cycling mast cells, concomitant reduction T H 17 cells. Ligand–receptor expression uncovers eosinophil recruitment programs, increased fibroblast disease, IL-9 IL-4 IL-13 2 endothelial as potential interactors. Resolution inflammation-associated signatures includes CD4 RM contraction type-specific downregulation chemoattractant, growth, survival factors. These cellular remission advance our understanding inflammation opportunities for therapeutic intervention.