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Introduction Characterising interactions between intestinal adaptive immune cells and their microenvironment is essential to understand drivers of intestinal remodelling in coeliac disease (CeD). We previously used spatial transcriptomics (ST) to identify putative lymphoid structures in CeD (FitzPatrick et al., Nature Immunology 2025), representing sites of putative gluten-specific T-B cell interactions. However, these structures have not been described at single cell resolution, limiting our understanding of their role in CeD. We sought to profile the spatial landscape of the coeliac duodenum, focusing on adaptive immune responses and epithelial barrier function.Methods We performed sub-cellular resolution imaging-based ST (Xenium, 10x Genomics) on 18 duodenal biopsy sections (active CeD (ACD), n=7; treated CeD (TCD), n=5; non-coeliac controls (NCC), n=6) with a targeted panel of 322 genes. We validated and extended this dataset with a further ST experiment featuring 20 sections (ACD, n=7; TCD, n=7; NCC, n=6) profiled with a panel of 5101 genes.Results Our first ST experiment yielded a dataset of over 30 million transcripts detected across 385,384 cells, representing epithelial, stromal, immune, endothelial, and secretory compartments. We identified lymphoid aggregates in both ACD and TCD, in some cases exhibiting organised structure with separate T- and B-cell areas and evidence of germinal centre activity.Our second experiment with a larger gene panel expands our data with an additional 150 million transcripts detected across 462,030 cells representing all major small intestinal cell types. Epithelial gene expression demonstrated spatial zonation of absorptive and metabolic function along the crypt-villus axis which was altered in ACD. The epithelium was supported by sub-epithelial stromal telocytes, which were reduced in ACD.Lymphoid aggregates (LA) containing B cells and CD4+ T cells were present in several CeD samples in both datasets, but less common in controls. Aggregates displayed various levels of organisation, with larger aggregates often extending into the submucosa. CeD samples contained distinct macrophage populations that localised to epithelial lesions and LA. LA also featured stromal cells resembling fibroblastic reticular cells, previously implicated in inflammatory bowel disease (Kinchen et al., Cell 2018), as well as follicular-associated epithelium (M cells), which may be involved in luminal antigen presentation.Conclusions We used spatial transcriptomics to localise cellular interactions and disease processes in the duodenum in CeD, specifically lymphoid aggregates as the site of T-B cell interactions. We link this with changes in tissue structure and function.