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@ARTICLE{Jakob:282558,
author = {Jakob, Manuel O and Sterczyk, Nele and Boulekou, Sotiria
and Forster, Patrycja M and Barleben, Luisa and Alzain,
Nadra and Jarick, Katja J and Pirzgalska, Roksana M and
Raposo, Bruno and Hansson, Karl and Nyström, Elisabeth E L
and Gondrand, Aurelia and González-Acera, Miguel and
Leclère, Pierre S and Lapson, Marlen S and Poggenseier,
Sarah and Deshpande, Divija and Velleman, Laura and
Breiderhoff, Tilman and Brunkhorst, Max Felix and Schüle,
Anton M and Guerra, Gabriela M and Durek, Pawel and
Mashreghi, Mir-Farzin and Kühl, Anja A and Chu, Coco and
Schneider, Christoph and Weidinger, Carl and Siegmund,
Britta and Nordmann, Thierry M and Voehringer, David and
Patankar, Jay V and Becker, Christoph and Birchenough,
George M H and Veiga-Fernandes, Henrique and Ronchi,
Francesca and Kolesnichenko, Marina and Diefenbach, Andreas
and Klose, Christoph S N},
title = {{E}nteric nervous system-derived {VIP} restrains
differentiation of {LGR}5+ stem cells toward the secretory
lineage impeding type 2 immune programs.},
journal = {Nature immunology},
volume = {26},
number = {12},
issn = {1529-2908},
address = {London},
publisher = {Springer Nature Limited},
reportid = {DZNE-2025-01321},
pages = {2227 - 2243},
year = {2025},
abstract = {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.},
keywords = {Animals / Vasoactive Intestinal Peptide: metabolism /
Vasoactive Intestinal Peptide: immunology / Enteric Nervous
System: immunology / Enteric Nervous System: metabolism /
Cell Differentiation: immunology / Mice / Receptors,
G-Protein-Coupled: metabolism / Cell Lineage / Intestinal
Mucosa: immunology / Intestinal Mucosa: metabolism /
Lymphocytes: immunology / Immunity, Innate / Mice, Inbred
C57BL / Stem Cells: immunology / Stem Cells: metabolism /
Mice, Knockout / Homeostasis / Vasoactive Intestinal Peptide
(NLM Chemicals) / Receptors, G-Protein-Coupled (NLM
Chemicals) / Lgr5 protein, mouse (NLM Chemicals)},
cin = {AG Wurst},
ddc = {610},
cid = {I:(DE-2719)1140001},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41286457},
doi = {10.1038/s41590-025-02325-1},
url = {https://pub.dzne.de/record/282558},
}