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This study validates that patient-derived esophageal organoids treated with IL-13 accurately replicate key epithelial abnormalities observed in eosinophilic esophagitis (EoE), including disrupted cell differentiation, impaired maturation, and inflammatory signaling. Using single-cell RNA sequencing, researchers identified seven distinct epithelial cell types preserved in both patient biopsies and organoids, demonstrating that IL-13 alone can reproduce the epithelial developmental defects characteristic of EoE. However, patient biopsies showed additional immune and tissue remodeling changes not captured by IL-13 treatment alone, indicating other factors contribute to the full disease state.
Why it matters
This organoid model provides researchers with a controlled laboratory system to study the epithelial mechanisms of eosinophilic esophagitis and test potential therapies without requiring repeated patient biopsies. The findings confirm IL-13 as a central driver of epithelial dysfunction in EoE, which could inform targeted therapeutic strategies for this chronic inflammatory condition.
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⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
Background and Aims: Eosinophilic esophagitis (EoE) features prominent epithelial dysregulation that persists despite resolution of eosinophilia. Interleukin-13 (IL-13) is known to be a key upstream driver of epithelial abnormalities in EoE. We sought to benchmark an IL-13 esophageal organoid model against the in vivo epithelial state in EoE at a single cell resolution, to define in the role of IL-13 in aberrant epithelial development and inflammation in EoE, and to validate the IL-13 organoid as a model system to study the epithelial changes seen in EoE. Methods: We performed scRNA-Seq on esophageal biopsies from control and EoE patients, and esophageal biopsy-derived organoids with or without IL-13. We compared cellular composition, differentiation trajectories, pathway enrichment, and differential gene expression within both systems, and assessed findings at a protein level. Results: Seven distinct epithelial cell clusters were identified and preserved in both biopsies and organoids. EoE biopsies demonstrated expansion of cycling cells, whereas IL-13-treated organoids showed shift in the composition of the suprabasal compartments. Pseudotime topology was preserved across tissues, with a shift away from terminal differentiation in both EoE biopsies and IL-13-treated organoids. IL-13 reproduced changes in the transcription of central EoE genes and the dysregulation of epithelial proliferation and differentiation pathways seen in EoE. There was broad activation of immune related pathways within both EoE biopsies and IL-13-treated organoids, however, biopsies additionally showed activation in several immune and extracellular matrix remodeling programs that IL-13 alone did not reproduce. Conclusion: IL-13-treated esophageal organoids replicate key epithelial features of EoE including dysregulated epithelial development, impaired cornification, and inflammatory signals, while preserving lineage architecture, providing a tractable platform for epithelial-targeted mechanistic and therapeutic studies.