Oral Presentation International Celiac Disease Symposium 2026

High resolution spatial transcriptomics reveals changes in barrier function and stromal-epithelial-immune interactions in celiac disease (146760)

Karolina Künnapuu 1 2 , Paul Klenerman 1 , Agne Antanaviciute 2 3 , Michael E.B. FitzPatrick 1
  1. Translational Gastroenterology and Liver Unit, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
  2. Centre for Computational Biology, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom
  3. Translational Immune Discovery Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom

Background and Aims

Characterising how the epithelial barrier interacts with its surrounding microenvironment is essential for understanding intestinal remodelling in celiac disease (CeD). We previously used low resolution spatial transcriptomics (ST) to localise disease processes within the intestinal mucosa, describing changes in epithelial gene expression and identifying lymphoid aggregates as potential sites of gluten-specific immune interactions (1). We sought to perform sub-cellular resolution mapping of the CeD duodenum, focusing on how immune and stromal cells influence epithelial function.

Materials and Methods

We performed sub-cellular resolution imaging-based ST (Xenium, 10x Genomics) on 40 duodenal biopsy sections (active CeD (ACD), n=16; treated CeD (TCD), n=10; potential CeD (PCD), n=3; non-celiac controls (NCC), n=11) with a panel of 5101 genes.

Results

Our dataset of 170 million transcripts across more than 800,000 cells allowed detailed mapping of CeD-associated changes to the digestive and protective functions of the epithelium along the crypt-villus axis, including zonated changes to immune response and absorption pathways and localised shifts toward a gastric phenotype. We linked these changes with phenotypic shifts in surrounding stromal cells and matrix metalloproteinase (MMP)-expressing macrophages which may contribute to remodelling through persistent inflammation, wound-healing responses, and changes in extracellular matrix organisation. We identified further lymphoid aggregates in both ACD and TCD, in some cases exhibiting follicle-like structure with separate T- and B-cell areas, dendritic cells, MMP-expressing macrophages, and a specialised epithelium with antigen-presenting capacity (M cells) as well as pro-inflammatory stromal populations associated with lymphoid follicle formation in other autoimmune conditions (2).

Conclusions

Using ST, we have characterised crosstalk with stromal and immune cells as a driver of epithelial reprogramming and tissue remodelling and identified lymphoid aggregates as specialised sites of adaptive immune activity in CeD.

  1. FitzPatrick, M.E.B. et al. (2025) ‘Immune–epithelial–stromal networks define the cellular ecosystem of the small intestine in celiac disease’, Nature Immunology, pp. 1–16.
  2. Kinchen, J. et al. (2018) ‘Structural Remodeling of the Human Colonic Mesenchyme in Inflammatory Bowel Disease’, Cell, 175(2), pp. 372-386.e17.