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000282558 0247_ $$2ISSN$$a1529-2916
000282558 037__ $$aDZNE-2025-01321
000282558 041__ $$aEnglish
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000282558 1001_ $$00000-0003-3638-3114$$aJakob, Manuel O$$b0
000282558 245__ $$aEnteric nervous system-derived VIP restrains differentiation of LGR5+ stem cells toward the secretory lineage impeding type 2 immune programs.
000282558 260__ $$aLondon$$bSpringer Nature Limited$$c2025
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000282558 520__ $$aBarrier 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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000282558 650_7 $$037221-79-7$$2NLM Chemicals$$aVasoactive Intestinal Peptide
000282558 650_7 $$2NLM Chemicals$$aReceptors, G-Protein-Coupled
000282558 650_7 $$2NLM Chemicals$$aLgr5 protein, mouse
000282558 650_2 $$2MeSH$$aAnimals
000282558 650_2 $$2MeSH$$aVasoactive Intestinal Peptide: metabolism
000282558 650_2 $$2MeSH$$aVasoactive Intestinal Peptide: immunology
000282558 650_2 $$2MeSH$$aEnteric Nervous System: immunology
000282558 650_2 $$2MeSH$$aEnteric Nervous System: metabolism
000282558 650_2 $$2MeSH$$aCell Differentiation: immunology
000282558 650_2 $$2MeSH$$aMice
000282558 650_2 $$2MeSH$$aReceptors, G-Protein-Coupled: metabolism
000282558 650_2 $$2MeSH$$aCell Lineage
000282558 650_2 $$2MeSH$$aIntestinal Mucosa: immunology
000282558 650_2 $$2MeSH$$aIntestinal Mucosa: metabolism
000282558 650_2 $$2MeSH$$aLymphocytes: immunology
000282558 650_2 $$2MeSH$$aImmunity, Innate
000282558 650_2 $$2MeSH$$aMice, Inbred C57BL
000282558 650_2 $$2MeSH$$aStem Cells: immunology
000282558 650_2 $$2MeSH$$aStem Cells: metabolism
000282558 650_2 $$2MeSH$$aMice, Knockout
000282558 650_2 $$2MeSH$$aHomeostasis
000282558 7001_ $$aSterczyk, Nele$$b1
000282558 7001_ $$aBoulekou, Sotiria$$b2
000282558 7001_ $$aForster, Patrycja M$$b3
000282558 7001_ $$aBarleben, Luisa$$b4
000282558 7001_ $$aAlzain, Nadra$$b5
000282558 7001_ $$00000-0001-5162-7266$$aJarick, Katja J$$b6
000282558 7001_ $$aPirzgalska, Roksana M$$b7
000282558 7001_ $$00000-0003-4734-7207$$aRaposo, Bruno$$b8
000282558 7001_ $$aHansson, Karl$$b9
000282558 7001_ $$aNyström, Elisabeth E L$$b10
000282558 7001_ $$00009-0004-9989-4899$$aGondrand, Aurelia$$b11
000282558 7001_ $$aGonzález-Acera, Miguel$$b12
000282558 7001_ $$00000-0002-1794-9461$$aLeclère, Pierre S$$b13
000282558 7001_ $$aLapson, Marlen S$$b14
000282558 7001_ $$00009-0001-5343-9987$$aPoggenseier, Sarah$$b15
000282558 7001_ $$00000-0001-9166-2509$$aDeshpande, Divija$$b16
000282558 7001_ $$00009-0002-7347-8067$$aVelleman, Laura$$b17
000282558 7001_ $$0P:(DE-2719)9003035$$aBreiderhoff, Tilman$$b18
000282558 7001_ $$aBrunkhorst, Max Felix$$b19
000282558 7001_ $$00009-0003-3094-9778$$aSchüle, Anton M$$b20
000282558 7001_ $$aGuerra, Gabriela M$$b21
000282558 7001_ $$00000-0002-6179-0670$$aDurek, Pawel$$b22
000282558 7001_ $$00000-0002-8015-6907$$aMashreghi, Mir-Farzin$$b23
000282558 7001_ $$00000-0003-2293-5387$$aKühl, Anja A$$b24
000282558 7001_ $$aChu, Coco$$b25
000282558 7001_ $$00000-0002-0452-2960$$aSchneider, Christoph$$b26
000282558 7001_ $$00000-0002-9948-0088$$aWeidinger, Carl$$b27
000282558 7001_ $$00000-0002-0055-958X$$aSiegmund, Britta$$b28
000282558 7001_ $$aNordmann, Thierry M$$b29
000282558 7001_ $$00000-0001-6650-0639$$aVoehringer, David$$b30
000282558 7001_ $$aPatankar, Jay V$$b31
000282558 7001_ $$00000-0002-1388-1041$$aBecker, Christoph$$b32
000282558 7001_ $$aBirchenough, George M H$$b33
000282558 7001_ $$00000-0001-6216-1836$$aVeiga-Fernandes, Henrique$$b34
000282558 7001_ $$aRonchi, Francesca$$b35
000282558 7001_ $$00000-0001-7366-9061$$aKolesnichenko, Marina$$b36
000282558 7001_ $$00000-0002-9176-9530$$aDiefenbach, Andreas$$b37
000282558 7001_ $$00000-0001-8803-2979$$aKlose, Christoph S N$$b38
000282558 773__ $$0PERI:(DE-600)2026412-4$$a10.1038/s41590-025-02325-1$$gVol. 26, no. 12, p. 2227 - 2243$$n12$$p2227 - 2243$$tNature immunology$$v26$$x1529-2908$$y2025
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