Fibroblast 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.
Authors
- Ole Haagen Nielsen (ORCID: https://orcid.org/0000-0003-4612-8635)
- Grigorii Nos (ORCID: https://orcid.org/0000-0002-8066-7424)
- Søren Brunak (ORCID: https://orcid.org/0000-0003-0316-5866)
- William W. Agace (ORCID: https://orcid.org/0000-0003-3823-5772)
- Peter Leth Jørgensen (ORCID: https://orcid.org/0000-0001-5262-0074)
- Henrik Jakobsen (ORCID: https://orcid.org/0000-0001-5611-6692)
- Fredrik Junghus (ORCID: https://orcid.org/0000-0002-8828-5375)
- Urs Mörbe (ORCID: https://orcid.org/0000-0001-8747-437X)
- Lars Rønn Olsen (ORCID: https://orcid.org/0000-0002-6725-7850)
- Mads Damsgaard Wewer (ORCID: https://orcid.org/0000-0001-9140-9706)
- Gorm Roager Madsen (ORCID: https://orcid.org/0000-0001-5525-7338)
- Lene Riis (ORCID: https://orcid.org/0000-0003-4669-3159)
- Melissa J. Ensmenger (ORCID: https://orcid.org/0009-0002-5561-9815)
- Venla A. Väänänen (ORCID: https://orcid.org/0000-0002-6366-1610)
Institutions
- University of Copenhagen (DK)
- Lund University (SE)
- Novo Nordisk Foundation (DK)
- Herlev Hospital (DK)
- Hvidovre Hospital (DK)
- Copenhagen University Hospital (DK)
- LEO Foundation (DK)
- Technical University of Denmark (DK)
Publication Details
- Journal
- The Journal of Experimental Medicine
- Published
- 2025-11-19
- DOI
- https://doi.org/10.1084/jem.20250471
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 0.00