![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
Tools
Tools
| Item Type: | Article |
|---|---|
| Title: | Enteric nervous system-derived VIP restrains differentiation of LGR(5)(+) stem cells toward the secretory lineage impeding type 2 immune programs |
| Creators: |
Jakob, Manuel O.  ORCID: https://orcid.org/0000-0003-3638-3114, Sterczyk, Nele, Boulekou, Sotiria, Forster, Patrycja M., Barleben, Luisa ORCID: https://orcid.org/0000-0002-0400-7117, Alzain, Nadra, Jarick, Katja J. ORCID: https://orcid.org/0000-0001-5162-7266, Pirzgalska, Roksana M., Raposo, Bruno ORCID: https://orcid.org/0000-0003-4734-7207, Hansson, Karl, Nyström, Elisabeth E.L., Gondrand, Aurelia ORCID: https://orcid.org/0009-0004-9989-4899, González-Acera, Miguel, Leclère, Pierre S. ORCID: https://orcid.org/0000-0002-1794-9461, Lapson, Marlen S., Poggenseier, Sarah ORCID: https://orcid.org/0009-0001-5343-9987, Deshpande, Divija ORCID: https://orcid.org/0000-0001-9166-2509, Velleman, Laura ORCID: https://orcid.org/0009-0002-7347-8067, Breiderhoff, Tilman ORCID: https://orcid.org/0000-0002-1676-7498, Brunkhorst, Max Felix, Schüle, Anton M. ORCID: https://orcid.org/0009-0003-3094-9778, Guerra, Gabriela M., Durek, Pawel ORCID: https://orcid.org/0000-0002-6179-0670, Mashreghi, Mir-Farzin ORCID: https://orcid.org/0000-0002-8015-6907, Kühl, Anja A. ORCID: https://orcid.org/0000-0003-2293-5387, Chu, Coco, Schneider, Christoph ORCID: https://orcid.org/0000-0002-0452-2960, Weidinger, Carl ORCID: https://orcid.org/0000-0002-9948-0088, Siegmund, Britta ORCID: https://orcid.org/0000-0002-0055-958X, Nordmann, Thierry M., Voehringer, David ORCID: https://orcid.org/0000-0001-6650-0639, Patankar, Jay V., Becker, Christoph ORCID: https://orcid.org/0000-0002-1388-1041, Birchenough, George M.H., Veiga-Fernandes, Henrique ORCID: https://orcid.org/0000-0001-6216-1836, Ronchi, Francesca, Kolesnichenko, Marina ORCID: https://orcid.org/0000-0001-7366-9061, Diefenbach, Andreas ORCID: https://orcid.org/0000-0002-9176-9530 and Klose, Christoph S.N. ORCID: https://orcid.org/0000-0001-8803-2979
|
| 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: | Cell Differentiation, Cell Lineage, Enteric Nervous System, G-Protein-Coupled Receptors, Homeostasis, Inbred C57BL Mice, Innate Immunity, Intestinal Mucosa, Knockout Mice, Lymphocytes, Stem Cells, Vasoactive Intestinal Peptide, Animals |
| Source: | Nature Immunology |
| ISSN: | 1529-2908 |
| Publisher: | Nature Publishing Group |
| Volume: | 26 |
| Number: | 12 |
| Page Range: | 2227-2243 |
| Date: | December 2025 |
| Official Publication: | https://doi.org/10.1038/s41590-025-02325-1 |
| PubMed: | View item in PubMed |
| Related to: |
Repository Staff Only: item control page
