a, Gene score of chemokines across MGN and INFLAREs from the stomach, duodenum and ileum across different conditions. b, Cell–cell interactions mediated by CXCL chemokines expressed by INFLAREs and various immune cells or venous endothelial cells (ECs). MAIT, mucosal-associated invariant T cell; TEM, effector memory T cell; TH17, T helper 17 cell; Treg, regulatory T cell; TRM, tissue resident memory T cell. c, smFISH staining of INFLARE (MUC6 and BPIFB1), surface foveolar (MUC5AC) and activated endothelial (ACKR1) cells showing the proximity of vessels to metaplastic glands in Crohn’s disease duodenum. Representative image from n = 3. Scale bars, 100 µm. White arrows highlight ACKR1+ vessels, yellow arrows indicate BPIFB1+MUC6+ cells. For both images, the scale bar represents 100 μm. d, Gene score of MHC class II genes and peptide processing genes across MGN and INFLAREs from the stomach, duodenum and ileum across different conditions. e, Protein staining of INFLAREs (MUC6), macrophages (CD68) and MHC class II (HLA-DR) in the ileum from a Crohn’s disease resection showing high MHC class II expression in INFLAREs. Representative image from n = 2. f, Schematic of the signalling pathway from IFNγR to MHC class II (left), with a dotplot of gene scores from this pathway in MGN and INFLAREs from the stomach, duodenum and ileum across different conditions (right). Schematics in panel f were created with BioRender (https://biorender.com). g, Protein staining of INFLAREs (MUC6), CD4 T cells (CD3+CD4+), CD8 T cells (CD8+CD3+) and γδ T cells (TCRγδ+CD3+) in Crohn’s disease ileum, showing interaction between CD4 T cells and INFLAREs. Representative image from n = 4. Scale bars, 100 µm. h, Schematic of the potential role of pyloric metaplasia in inflammatory intestinal diseases. INFLAREs arise in response to local inflammation to promote mucosal healing via mucous and antimicrobial peptide secretion. As disease progresses, INFLAREs contribute to ongoing inflammation through association with activated vessels, the recruitment of various immune cells and direct interactions with CD4+ T cells via MHC class II.