Home > Publications Database > Enteric nervous system-derived VIP restrains differentiation of LGR5+ stem cells toward the secretory lineage impeding type 2 immune programs. > print

001     282558
005     20251219103450.0
024 7 _ |a 10.1038/s41590-025-02325-1
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024 7 _ |a 1529-2908
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024 7 _ |a 1529-2916
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037 _ _ |a DZNE-2025-01321
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Jakob, Manuel O
|0 0000-0003-3638-3114
|b 0
245 _ _ |a Enteric nervous system-derived VIP restrains differentiation of LGR5+ stem cells toward the secretory lineage impeding type 2 immune programs.
260 _ _ |a London
|c 2025
|b Springer Nature Limited
336 7 _ |a article
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336 7 _ |a ARTICLE
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336 7 _ |a Journal Article
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520 _ _ |a Barrier homeostasis relies on a finely tuned interplay between the immune system, epithelial cells and commensal microbiota. Beyond these regulators, the enteric nervous system has recently emerged as a central hub coordinating intestinal immune responses, although its role in epithelial differentiation has remained largely unexplored. Here, we identify a neuroepithelial circuit in which vasoactive intestinal peptide (VIP)-positive enteric neurons act on VIPR1+ epithelial stem cells to restrain both their proliferation and secretory lineage differentiation. Disruption of this pathway leads to an expansion of tuft cells, enhanced interleukin (IL)-25 production, activation of group 2 innate lymphoid cells (ILC2s) and induction of a type 2 immune response resembling worm expulsion. This phenotype occurs independently of the microbiota but is modulated by the IL-25R-ILC2-IL-13 axis and dietary solid food intake. Our findings expose the enteric nervous system as a critical regulator of epithelial fate decisions and immune balance, complementing established mechanisms that safeguard barrier integrity and mucosal homeostasis.
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588 _ _ |a Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
650 _ 7 |a Vasoactive Intestinal Peptide
|0 37221-79-7
|2 NLM Chemicals
650 _ 7 |a Receptors, G-Protein-Coupled
|2 NLM Chemicals
650 _ 7 |a Lgr5 protein, mouse
|2 NLM Chemicals
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Vasoactive Intestinal Peptide: metabolism
|2 MeSH
650 _ 2 |a Vasoactive Intestinal Peptide: immunology
|2 MeSH
650 _ 2 |a Enteric Nervous System: immunology
|2 MeSH
650 _ 2 |a Enteric Nervous System: metabolism
|2 MeSH
650 _ 2 |a Cell Differentiation: immunology
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Receptors, G-Protein-Coupled: metabolism
|2 MeSH
650 _ 2 |a Cell Lineage
|2 MeSH
650 _ 2 |a Intestinal Mucosa: immunology
|2 MeSH
650 _ 2 |a Intestinal Mucosa: metabolism
|2 MeSH
650 _ 2 |a Lymphocytes: immunology
|2 MeSH
650 _ 2 |a Immunity, Innate
|2 MeSH
650 _ 2 |a Mice, Inbred C57BL
|2 MeSH
650 _ 2 |a Stem Cells: immunology
|2 MeSH
650 _ 2 |a Stem Cells: metabolism
|2 MeSH
650 _ 2 |a Mice, Knockout
|2 MeSH
650 _ 2 |a Homeostasis
|2 MeSH
700 1 _ |a Sterczyk, Nele
|b 1
700 1 _ |a Boulekou, Sotiria
|b 2
700 1 _ |a Forster, Patrycja M
|b 3
700 1 _ |a Barleben, Luisa
|b 4
700 1 _ |a Alzain, Nadra
|b 5
700 1 _ |a Jarick, Katja J
|0 0000-0001-5162-7266
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700 1 _ |a Pirzgalska, Roksana M
|b 7
700 1 _ |a Raposo, Bruno
|0 0000-0003-4734-7207
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700 1 _ |a Hansson, Karl
|b 9
700 1 _ |a Nyström, Elisabeth E L
|b 10
700 1 _ |a Gondrand, Aurelia
|0 0009-0004-9989-4899
|b 11
700 1 _ |a González-Acera, Miguel
|b 12
700 1 _ |a Leclère, Pierre S
|0 0000-0002-1794-9461
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700 1 _ |a Lapson, Marlen S
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700 1 _ |a Poggenseier, Sarah
|0 0009-0001-5343-9987
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700 1 _ |a Deshpande, Divija
|0 0000-0001-9166-2509
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700 1 _ |a Velleman, Laura
|0 0009-0002-7347-8067
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700 1 _ |a Breiderhoff, Tilman
|0 P:(DE-2719)9003035
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700 1 _ |a Brunkhorst, Max Felix
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700 1 _ |a Schüle, Anton M
|0 0009-0003-3094-9778
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700 1 _ |a Guerra, Gabriela M
|b 21
700 1 _ |a Durek, Pawel
|0 0000-0002-6179-0670
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700 1 _ |a Mashreghi, Mir-Farzin
|0 0000-0002-8015-6907
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700 1 _ |a Kühl, Anja A
|0 0000-0003-2293-5387
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700 1 _ |a Chu, Coco
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700 1 _ |a Schneider, Christoph
|0 0000-0002-0452-2960
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700 1 _ |a Weidinger, Carl
|0 0000-0002-9948-0088
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700 1 _ |a Siegmund, Britta
|0 0000-0002-0055-958X
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700 1 _ |a Nordmann, Thierry M
|b 29
700 1 _ |a Voehringer, David
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700 1 _ |a Patankar, Jay V
|b 31
700 1 _ |a Becker, Christoph
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|b 32
700 1 _ |a Birchenough, George M H
|b 33
700 1 _ |a Veiga-Fernandes, Henrique
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700 1 _ |a Ronchi, Francesca
|b 35
700 1 _ |a Kolesnichenko, Marina
|0 0000-0001-7366-9061
|b 36
700 1 _ |a Diefenbach, Andreas
|0 0000-0002-9176-9530
|b 37
700 1 _ |a Klose, Christoph S N
|0 0000-0001-8803-2979
|b 38
773 _ _ |a 10.1038/s41590-025-02325-1
|g Vol. 26, no. 12, p. 2227 - 2243
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|t Nature immunology
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|y 2025
|x 1529-2908
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