| Title: |
Immune–epithelial–stromal networks define the cellular ecosystem of the small intestine in celiac disease |
| Authors: |
FitzPatrick, MEB; Antanaviciute, A; Dunstan, M; Künnapuu, K; Trzupek, D; Provine, NM; Dooley, K; Zhang, J-Y; Irwin, SL; Garner, LC; Pernes, JI; Ferreira, RC; Sasson, SC; Aschenbrenner, D; Agarwal, D; Rodrigues, A; Howarth, L; Brain, O; Ruane, D; Soilleux, E; Teichmann, SA; Dendrou, CA; Simmons, A; Uhlig, HH; Todd, JA; Klenerman, P |
| Publisher Information: |
Springer Nature |
| Publication Year: |
2025 |
| Collection: |
Oxford University Research Archive (ORA) |
| Description: |
The immune–epithelial–stromal interactions underpinning intestinal damage in celiac disease (CD) are incompletely understood. To address this, we performed single-cell transcriptomics (RNA sequencing; 86,442 immune, parenchymal and epithelial cells; 35 participants) and spatial transcriptomics (20 participants) on CD intestinal biopsy samples. Here we show that in CD, epithelial populations shifted toward a progenitor state, with interferon-driven transcriptional responses, and perturbation of secretory and enteroendocrine populations. Mucosal T cells showed numeric and functional changes in regulatory and follicular helper-like CD4+ T cells, intraepithelial lymphocytes, CD8+ and γδ T cell subsets, with skewed T cell antigen receptor repertoires. Mucosal changes remained detectable despite treatment, representing a persistent immune–epithelial ‘scar’. Spatial transcriptomics defined transcriptional niches beyond those captured in conventional histological scores, including CD-specific lymphoid aggregates containing T cell–B cell interactions. Receptor–ligand spatial analyses integrated with disease susceptibility gene expression defined networks of altered chemokine and morphogen signaling, and provide potential therapeutic targets for CD prevention and treatment. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1038/s41590-025-02146-2 |
| Availability: |
https://doi.org/10.1038/s41590-025-02146-2; https://ora.ox.ac.uk/objects/uuid:e8500c61-898a-49c6-b086-d22dcfd2c7bd |
| Rights: |
info:eu-repo/semantics/openAccess ; CC Attribution (CC BY) |
| Accession Number: |
edsbas.35939203 |
| Database: |
BASE |