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Fibroblast diversity within human gut-associated lymphoid tissues

Mörbe, Urs M LU ; Junghus, Fredrik V LU ; Nos, Grigorii LU ; Jørgensen, Peter B LU ; Ensmenger, Melissa J ; Väänänen, Venla A ; Wewer, Mads D ; Madsen, Gorm R ; Riis, Lene B and Jakobsen, Henrik L , et al. (2026) In The Journal of experimental medicine 223(3).
Abstract

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... (More)

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.

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type
Contribution to journal
publication status
published
subject
keywords
Humans, Fibroblasts/metabolism, Lymphoid Tissue/immunology, CD24 Antigen/metabolism, Peyer's Patches/immunology, Intestinal Mucosa/immunology, Single-Cell Analysis, Crohn Disease/pathology
in
The Journal of experimental medicine
volume
223
issue
3
article number
20250471
publisher
Rockefeller University Press
external identifiers
  • scopus:105024656082
  • pmid:41379085
ISSN
1540-9538
DOI
10.1084/jem.20250471
language
English
LU publication?
yes
additional info
© 2025 Mörbe et al.
id
3501b347-0607-4951-b435-8f7b69ec756f
date added to LUP
2025-12-29 10:56:41
date last changed
2026-01-13 05:39:20
@article{3501b347-0607-4951-b435-8f7b69ec756f,
  abstract     = {{<p>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.</p>}},
  author       = {{Mörbe, Urs M and Junghus, Fredrik V and Nos, Grigorii and Jørgensen, Peter B and Ensmenger, Melissa J and Väänänen, Venla A and Wewer, Mads D and Madsen, Gorm R and Riis, Lene B and Jakobsen, Henrik L and Olsen, Lars R and Brunak, Søren and Nielsen, Ole H and Agace, William W}},
  issn         = {{1540-9538}},
  keywords     = {{Humans; Fibroblasts/metabolism; Lymphoid Tissue/immunology; CD24 Antigen/metabolism; Peyer's Patches/immunology; Intestinal Mucosa/immunology; Single-Cell Analysis; Crohn Disease/pathology}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{3}},
  publisher    = {{Rockefeller University Press}},
  series       = {{The Journal of experimental medicine}},
  title        = {{Fibroblast diversity within human gut-associated lymphoid tissues}},
  url          = {{http://dx.doi.org/10.1084/jem.20250471}},
  doi          = {{10.1084/jem.20250471}},
  volume       = {{223}},
  year         = {{2026}},
}