biostudies-literatureMorbe UMNovo Nordisk FoundationLeona M. and Harry B. Helmsley Charitable TrustEuropean Crohn's and Colitis OrganisationLundbeck FoundationLouis-Hansen-Foundatione20250471https://www.ebi.ac.uk/biostudies/studies/S-EPMC12697342biostudies-literatureUnknown223(3)Gut-associated lymphoid tissues (GALT) represent major sites of adaptive immune priming in the intestine, yet our understanding of human GALT diversity and function remains limited. Here, we used single-cell RNA sequencing, flow cytometry, and confocal laser microscopy to map the fibroblast (FB) landscape of human GALT, including that of Peyer's patches (PP), mucosal isolated lymphoid follicles (M-ILF), and submucosal ILF (SM-ILF). We identify CD24 as a marker that distinguishes GALT from other intestinal FB and demonstrate that CD24+ FB consist of distinct subsets that locate within discrete niches. We show that the composition and transcriptional profile of M-ILF and SM-ILF FB differs with SM-ILF FB appearing more focused at providing T cell support. Finally, we find the transcription profile of PP T zone reticular cells to be altered in Crohn's disease and that cells with a GALT FB-like profile can be detected in other chronic inflammatory diseases. Collectively, our findings provide an important framework for understanding GALT diversity and function.The Journal of experimental medicineFibroblast diversity within human gut-associated lymphoid tissues.PMC12697342R155-2014-4184NNF22OC0071681Jakobsen HLNos GEnsmenger MJMadsen GRJunghus FVWewer MDMorbe UMBrunak SAgace WWVaananen VANielsen OHJorgensen PBOlsen LRRiis LBfalseFibroblast diversity within human gut-associated lymphoid tissues.Gut-associated lymphoid tissues (GALT) represent major sites of adaptive immune priming in the intestine, yet our understanding of human GALT diversity and function remains limited. Here, we used single-cell RNA sequencing, flow cytometry, and confocal laser microscopy to map the fibroblast (FB) landscape of human GALT, including that of Peyer's patches (PP), mucosal isolated lymphoid follicles (M-ILF), and submucosal ILF (SM-ILF). We identify CD24 as a marker that distinguishes GALT from other intestinal FB and demonstrate that CD24+ FB consist of distinct subsets that locate within discrete niches. We show that the composition and transcriptional profile of M-ILF and SM-ILF FB differs with SM-ILF FB appearing more focused at providing T cell support. Finally, we find the transcription profile of PP T zone reticular cells to be altered in Crohn's disease and that cells with a GALT FB-like profile can be detected in other chronic inflammatory diseases. Collectively, our findings provide an important framework for understanding GALT diversity and function.2026-01-01T00:00:00Z2026 Mar2026-05-26T14:04:57.996Z2026-05-24T03:12:25.448ZS-EPMC126973424137908510.1084/jem.20250471