Oral Presentation International Celiac Disease Symposium 2026

Single cell spatial transcriptomics reveals cellular neighbourhoods and immune architectures that distinguish active from treated coeliac disease (146853)

Olivia Moscatelli 1 , Linda Fothergill 1 , Alice Becker-Scott 1 2 , Karolina Künnapuu 3 4 , Ellen Tsui 1 , Raymond Yip 1 5 , Michael Christie 1 5 , Edwin Hawkins 1 5 , Agne Antanaviciute 4 6 , Michael Fitzpatrick 3 , Melinda Hardy 1 , Jason Tye-Din 1 2
  1. Walter and Eliza Hall Institute, Parkville, VIC, Australia
  2. Gastroenterology, The Royal Melbourne Hospital, Melbourne, VIC, Australia
  3. Translational Gastroenterology and Liver Unit, Nuffield Department of Medicine, University of Oxford, Oxford, Oxfordshire, England
  4. Centre for Computational Biology, Weatherall Institute of Medicine, University of Oxford, Oxford, Oxfordshire, England
  5. Colonial Foundation Diagnostics Centre, Melbourne, VIC, Australia
  6. Translational Immune Discovery Unit, Weatherall Institute of Medicine, University of Oxford, Oxford, Oxfordshire, England

Background: Recent single-cell and spatial studies have revealed complex immune-epithelial remodelling in coeliac disease (CeD), but the cellular neighbourhoods that distinguish active from treated disease remain incompletely defined. We used targeted single-cell spatial transcriptomics to resolve disease-state-specific cellular architecture in the duodenal mucosa.

Methods: Duodenal biopsies from 20 individuals (6 non-CeD controls, 9 active CeD, 5 treated CeD) were profiled using a custom 477-gene Xenium single-cell spatial transcriptomics panel (10x Genomics), supplemented with a 12-protein phenotyping panel.

Results: Active CeD demonstrated disease-state-specific remodelling of the mucosal cellular landscape compared with treated CeD, including expansion of plasma cells, CD4+ T cells and intraepithelial lymphocytes, together with reduced absorptive enterocytes at the villous tip. Neighbourhood-level spatial analysis revealed altered immune organisation in active CeD, with CD4+ T cells showing reduced proximity to epithelial and stromal cells and increased association with plasma cells compared with both treated CeD and non-CeD controls. Lymphoid aggregates were identified within the lamina propria of active and treated CeD samples, including structures with dense B-cell cores and transcriptional features consistent with tertiary lymphoid structures. These aggregates exhibited localised CXCL13-CXCR5 expression and broader CCR7-CCL19 expression patterns. Notably, CXCR5 and CCR7 were upregulated in CD4+ T cells in these structures, suggesting enrichment of T follicular helper-like programs that may support local B-cell responses.

Conclusions: Single-cell spatial transcriptomics identified a distinct cellular architecture in active CeD, characterised by altered immune cell composition and spatial reorganisation of cellular neighbourhoods. These findings demonstrate the utility of spatially resolved single-cell approaches for defining cellular neighbourhoods associated with mucosal disease activity. Ongoing experiments will extend this work to biopsies collected hours after oral gluten challenge to define the earliest spatial immune changes to gluten exposure.