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Heterogeneity of the intestinal mononuclear phagocyte compartment in health and inflammatory bowel disease

Fenton, Thomas M ; Wulff, Line ; Väänänen, Venla ; Jones, Gareth-Rhys ; Lemvigh, Camilla Koldbæk ; Riis, Lene B ; Wewer, Mads Damsgaard ; Vandamme, Julien ; Jørgensen, Peter B LU and Bain, Calum C , et al. (2025) In Science Immunology 10(114).
Abstract

Understanding of mononuclear phagocyte (MNP) diversity in the human intestine and the alterations this compartment undergoes in inflammation remains incomplete. Here, we used single-cell RNA sequencing, cellular indexing of trancriptomes and epitopes by sequencing, flow cytometry, and imaging to explore MNP heterogeneity in human ileal and colonic laminae propriae (LPs) in health and Crohn's disease (CD). In addition to monocytes, macrophage subsets, and conventional type 1 dendritic cells (cDC1s) and cDC2s, we found a CD1c + cDC subset with transcriptional features of DC3s. Using computational tools, we identified monocyte-to-macrophage trajectories as well as putative subset-specific DC precursors. We further showed that LP CCR7 +... (More)

Understanding of mononuclear phagocyte (MNP) diversity in the human intestine and the alterations this compartment undergoes in inflammation remains incomplete. Here, we used single-cell RNA sequencing, cellular indexing of trancriptomes and epitopes by sequencing, flow cytometry, and imaging to explore MNP heterogeneity in human ileal and colonic laminae propriae (LPs) in health and Crohn's disease (CD). In addition to monocytes, macrophage subsets, and conventional type 1 dendritic cells (cDC1s) and cDC2s, we found a CD1c + cDC subset with transcriptional features of DC3s. Using computational tools, we identified monocyte-to-macrophage trajectories as well as putative subset-specific DC precursors. We further showed that LP CCR7 + cDCs are increased in CD and provided evidence that these cells arise from intestinal cDC2s/DC3s but not cDC1s. Collectively, these findings extend our current understanding of intestinal MNP diversity and development, highlighting both tissue-specific and inflammation-induced changes in MNP composition and function.

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Contribution to journal
publication status
published
subject
keywords
Humans, Dendritic Cells/immunology, Inflammatory Bowel Diseases/immunology, Female, Male, Intestinal Mucosa/immunology, Macrophages/immunology, Crohn Disease/immunology, Phagocytes/immunology, Adult, Monocytes/immunology
in
Science Immunology
volume
10
issue
114
article number
eadz8650
publisher
American Association for the Advancement of Science (AAAS)
external identifiers
  • pmid:41385609
  • scopus:105024833718
ISSN
2470-9468
DOI
10.1126/sciimmunol.adz8650
language
English
LU publication?
yes
id
df1d4d30-73cf-4ffa-8357-37ecf2c0364c
date added to LUP
2025-12-29 10:57:29
date last changed
2026-01-27 06:13:59
@article{df1d4d30-73cf-4ffa-8357-37ecf2c0364c,
  abstract     = {{<p>Understanding of mononuclear phagocyte (MNP) diversity in the human intestine and the alterations this compartment undergoes in inflammation remains incomplete. Here, we used single-cell RNA sequencing, cellular indexing of trancriptomes and epitopes by sequencing, flow cytometry, and imaging to explore MNP heterogeneity in human ileal and colonic laminae propriae (LPs) in health and Crohn's disease (CD). In addition to monocytes, macrophage subsets, and conventional type 1 dendritic cells (cDC1s) and cDC2s, we found a CD1c + cDC subset with transcriptional features of DC3s. Using computational tools, we identified monocyte-to-macrophage trajectories as well as putative subset-specific DC precursors. We further showed that LP  CCR7 + cDCs are increased in CD and provided evidence that these cells arise from intestinal cDC2s/DC3s but not cDC1s. Collectively, these findings extend our current understanding of intestinal MNP diversity and development, highlighting both tissue-specific and inflammation-induced changes in MNP composition and function. </p>}},
  author       = {{Fenton, Thomas M and Wulff, Line and Väänänen, Venla and Jones, Gareth-Rhys and Lemvigh, Camilla Koldbæk and Riis, Lene B and Wewer, Mads Damsgaard and Vandamme, Julien and Jørgensen, Peter B and Bain, Calum C and Belling, Kirstine G and Ho, Gwo-Tzer and Pers, Tune H and Poulsen, Anja and Madsen, Gorm R and Nielsen, Ole H and Jakobsen, Henrik L and Izarzugaza, Jose Mg and Bendtsen, Flemming and Brunak, Søren and Mowat, Allan M and Olsen, Lars R and Mörbe, Urs and Agace, William W}},
  issn         = {{2470-9468}},
  keywords     = {{Humans; Dendritic Cells/immunology; Inflammatory Bowel Diseases/immunology; Female; Male; Intestinal Mucosa/immunology; Macrophages/immunology; Crohn Disease/immunology; Phagocytes/immunology; Adult; Monocytes/immunology}},
  language     = {{eng}},
  month        = {{12}},
  number       = {{114}},
  publisher    = {{American Association for the Advancement of Science (AAAS)}},
  series       = {{Science Immunology}},
  title        = {{Heterogeneity of the intestinal mononuclear phagocyte compartment in health and inflammatory bowel disease}},
  url          = {{http://dx.doi.org/10.1126/sciimmunol.adz8650}},
  doi          = {{10.1126/sciimmunol.adz8650}},
  volume       = {{10}},
  year         = {{2025}},
}