{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T13:04:17Z","timestamp":1794402257546,"version":"4.9.0"},"reference-count":56,"publisher":"Springer Science and Business Media LLC","issue":"8114","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nature"],"published-print":{"date-parts":[[2026,5,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Parasitic infections modulate both immune and sensory responses, but how these\u00a0systems collaborate to elicit protective behaviours remains incompletely understood. The gut epithelium contains specialized sensory cells that detect pathogens and irritants. These include cholinergic tuft cells, which sense parasites and initiate type 2 immune responses\n                    <jats:sup>1\u20133<\/jats:sup>\n                    , as well as serotonergic enterochromaffin (EC) cells, which detect irritants and communicate with afferent nerve fibres to transmit nociceptive signals\n                    <jats:sup>4\u20136<\/jats:sup>\n                    . Here we show that paracrine signalling between these cells constitutes a mechanism for neuro\u2013immune interaction and gut\u2013brain communication. We find that tuft cells use two distinct mechanisms of acetylcholine (ACh) release despite lacking synaptic vesicles and excitable membranes. These include acute release in response to parasite-derived metabolites, followed by constitutive \u2018leak-like\u2019 release, which occurs with type 2 inflammation. Although both mechanisms can activate muscarinic receptors on crypt-residing EC cells, only the sustained mode of ACh release elicits levels of serotonin sufficient to stimulate vagal afferent neurons that suppress food intake. This two-phase paracrine signalling mechanism explains how parasitic infection progresses from an initial asymptomatic phase to symptomatic established disease, in which type 2 immune and sensory signalling pathways within the gut\u2013brain axis collaborate to evoke protective behaviours.\n                  <\/jats:p>","DOI":"10.1038\/s41586-026-10281-5","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T16:02:04Z","timestamp":1774454524000},"page":"465-473","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Parasites trigger epithelial cell crosstalk to drive gut\u2013brain signalling"],"prefix":"10.1038","volume":"653","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3167-9784","authenticated-orcid":false,"given":"Kouki K.","family":"Touhara","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4018-2825","authenticated-orcid":false,"given":"Jinhao","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Castro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Erh","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guochuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Brizuela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea M.","family":"Harrington","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Garcia-Caraballo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracey","family":"O\u2019Donnell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Neumann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan D.","family":"Rossen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gudrun","family":"Schober","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9166-9919","authenticated-orcid":false,"given":"Yulong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5468-6867","authenticated-orcid":false,"given":"Richard M.","family":"Locksley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2527-2905","authenticated-orcid":false,"given":"Stuart M.","family":"Brierley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6365-4867","authenticated-orcid":false,"given":"David","family":"Julius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"key":"10281_CR1","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1038\/nature16527","volume":"529","author":"F Gerbe","year":"2016","unstructured":"Gerbe, F. et al. Intestinal epithelial tuft cells initiate type 2 mucosal immunity to helminth parasites. Nature 529, 226\u2013230 (2016).","journal-title":"Nature"},{"key":"10281_CR2","doi-asserted-by":"publisher","first-page":"1329","DOI":"10.1126\/science.aaf1648","volume":"351","author":"MR Howitt","year":"2016","unstructured":"Howitt, M. R. et al. Tuft cells, taste-chemosensory cells, orchestrate parasite type 2 immunity in the gut. Science 351, 1329\u20131333 (2016).","journal-title":"Science"},{"key":"10281_CR3","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1038\/nature16161","volume":"529","author":"J von Moltke","year":"2016","unstructured":"von Moltke, J., Ji, M., Liang, H. E. & Locksley, R. M. Tuft-cell-derived IL-25 regulates an intestinal ILC2\u2013epithelial response circuit. Nature 529, 221\u2013225 (2016).","journal-title":"Nature"},{"key":"10281_CR4","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1038\/s41586-023-05829-8","volume":"616","author":"JR Bayrer","year":"2023","unstructured":"Bayrer, J. R. et al. Gut enterochromaffin cells drive visceral pain and anxiety. Nature 616, 137\u2013142 (2023).","journal-title":"Nature"},{"key":"10281_CR5","doi-asserted-by":"publisher","first-page":"732","DOI":"10.1038\/s41586-024-08581-9","volume":"640","author":"KK Touhara","year":"2025","unstructured":"Touhara, K. K. et al. Topological segregation of stress sensors along the gut crypt-villus axis. Nature 640, 732\u2013742 (2025).","journal-title":"Nature"},{"key":"10281_CR6","doi-asserted-by":"publisher","first-page":"4298","DOI":"10.1016\/j.cell.2022.10.001","volume":"185","author":"Z Xie","year":"2022","unstructured":"Xie, Z. et al. The gut-to-brain axis for toxin-induced defensive responses. Cell 185, 4298\u20134316 (2022).","journal-title":"Cell"},{"key":"10281_CR7","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1146\/annurev-immunol-042718-041505","volume":"37","author":"CE O\u2019Leary","year":"2019","unstructured":"O\u2019Leary, C. E., Schneider, C. & Locksley, R. M. Tuft cells\u2014systemically dispersed sensory epithelia integrating immune and neural circuitry. Annu. Rev. Immunol. 37, 47\u201372 (2019).","journal-title":"Annu. Rev. Immunol."},{"key":"10281_CR8","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/j.cell.2017.05.034","volume":"170","author":"NW Bellono","year":"2017","unstructured":"Bellono, N. W. et al. Enterochromaffin cells are gut chemosensors that couple to sensory neural pathways. Cell 170, 185\u2013198 (2017).","journal-title":"Cell"},{"key":"10281_CR9","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.immuni.2020.10.014","volume":"54","author":"Z Chen","year":"2021","unstructured":"Chen, Z. et al. Interleukin-33 promotes serotonin release from enterochromaffin cells for intestinal homeostasis. Immunity 54, 151\u2013163 (2021).","journal-title":"Immunity"},{"key":"10281_CR10","doi-asserted-by":"publisher","first-page":"E7632","DOI":"10.1073\/pnas.1804938115","volume":"115","author":"C Alcaino","year":"2018","unstructured":"Alcaino, C. et al. A population of gut epithelial enterochromaffin cells is mechanosensitive and requires Piezo2 to convert force into serotonin release. Proc. Natl Acad. Sci. USA 115, E7632\u2013E7641 (2018).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"10281_CR11","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2501525122","volume":"122","author":"ND Rossen","year":"2025","unstructured":"Rossen, N. D. et al. Population imaging of enterochromaffin cell activity reveals regulation by somatostatin. Proc. Natl Acad. Sci. USA 122, e2501525122 (2025).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"10281_CR12","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1016\/S0140-6736(17)31930-X","volume":"391","author":"PM Jourdan","year":"2018","unstructured":"Jourdan, P. M., Lamberton, P. H. L., Fenwick, A. & Addiss, D. G. Soil-transmitted helminth infections. Lancet 391, 252\u2013265 (2018).","journal-title":"Lancet"},{"key":"10281_CR13","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1128\/CMR.05038-11","volume":"25","author":"SM Fletcher","year":"2012","unstructured":"Fletcher, S. M., Stark, D., Harkness, J. & Ellis, J. Enteric protozoa in the developed world: a public health perspective. Clin. Microbiol. Rev. 25, 420\u2013449 (2012).","journal-title":"Clin. Microbiol. Rev."},{"key":"10281_CR14","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.1016\/j.immuni.2024.03.023","volume":"57","author":"TE Billipp","year":"2024","unstructured":"Billipp, T. E. et al. Tuft cell-derived acetylcholine promotes epithelial chloride secretion and intestinal helminth clearance. Immunity 57, 1243\u20131259 (2024).","journal-title":"Immunity"},{"key":"10281_CR15","doi-asserted-by":"publisher","first-page":"1260","DOI":"10.1016\/j.immuni.2024.04.018","volume":"57","author":"M Ndjim","year":"2024","unstructured":"Ndjim, M. et al. Tuft cell acetylcholine is released into the gut lumen to promote anti-helminth immunity. Immunity 57, 1260\u20131273 (2024).","journal-title":"Immunity"},{"key":"10281_CR16","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1007\/BF00309889","volume":"262","author":"L Luciano","year":"1990","unstructured":"Luciano, L. & Reale, E. Brush cells of the mouse gallbladder. a correlative light- and electron-microscopical study. Cell Tissue Res. 262, 339\u2013349 (1990).","journal-title":"Cell Tissue Res."},{"key":"10281_CR17","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-01520-x","volume":"7","author":"B Hoover","year":"2017","unstructured":"Hoover, B. et al. The intestinal tuft cell nanostructure in 3D. Sci. Rep. 7, 1652 (2017).","journal-title":"Sci. Rep."},{"key":"10281_CR18","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1113\/jphysiol.2010.199976","volume":"589","author":"T Yajima","year":"2011","unstructured":"Yajima, T., Inoue, R., Matsumoto, M. & Yajima, M. Non-neuronal release of ACh plays a key role in secretory response to luminal propionate in rat colon. J. Physiol. 589, 953\u2013962 (2011).","journal-title":"J. Physiol."},{"key":"10281_CR19","first-page":"87","volume":"6","author":"B Schutz","year":"2015","unstructured":"Schutz, B. et al. Chemical coding and chemosensory properties of cholinergic brush cells in the mouse gastrointestinal and biliary tract. Front. Physiol. 6, 87 (2015).","journal-title":"Front. Physiol."},{"key":"10281_CR20","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1038\/s41592-024-02188-8","volume":"21","author":"F Deng","year":"2024","unstructured":"Deng, F. et al. Improved green and red GRAB sensors for monitoring spatiotemporal serotonin release in vivo. Nat. Methods 21, 692\u2013702 (2024).","journal-title":"Nat. Methods"},{"key":"10281_CR21","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.78512","volume":"12","author":"M Hayashi","year":"2023","unstructured":"Hayashi, M. et al. Enteroendocrine cell lineages that differentially control feeding and gut motility. eLife 12, e78512 (2023).","journal-title":"eLife"},{"key":"10281_CR22","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.immuni.2018.06.016","volume":"49","author":"MS Nadjsombati","year":"2018","unstructured":"Nadjsombati, M. S. et al. Detection of succinate by intestinal tuft cells triggers a type 2 innate immune circuit. Immunity 49, 33\u201341 (2018).","journal-title":"Immunity"},{"key":"10281_CR23","doi-asserted-by":"publisher","first-page":"5552","DOI":"10.1073\/pnas.1720758115","volume":"115","author":"W Lei","year":"2018","unstructured":"Lei, W. et al. Activation of intestinal tuft cell-expressed Sucnr1 triggers type 2 immunity in the mouse small intestine. Proc. Natl Acad. Sci. USA 115, 5552\u20135557 (2018).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"10281_CR24","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/j.cell.2018.05.014","volume":"174","author":"C Schneider","year":"2018","unstructured":"Schneider, C. et al. A metabolite-triggered tuft cell\u2013ILC2 circuit drives small intestinal remodeling. Cell 174, 271\u2013284 (2018).","journal-title":"Cell"},{"key":"10281_CR25","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1038\/s41583-022-00577-6","volume":"23","author":"Z Wu","year":"2022","unstructured":"Wu, Z., Lin, D. & Li, Y. Pushing the frontiers: tools for monitoring neurotransmitters and neuromodulators. Nat. Rev. Neurosci. 23, 257\u2013274 (2022).","journal-title":"Nat. Rev. Neurosci."},{"key":"10281_CR26","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1038\/s41594-021-00607-4","volume":"28","author":"Z Ruan","year":"2021","unstructured":"Ruan, Z. et al. Structures of the TRPM5 channel elucidate mechanisms of activation and inhibition. Nat. Struct. Mol. Biol. 28, 604\u2013613 (2021).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"10281_CR27","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-61878-9","volume":"16","author":"JR Buissant des Amorie","year":"2025","unstructured":"Buissant des Amorie, J. R. et al. Intestinal tuft cell subtypes represent successive stages of maturation driven by crypt-villus signaling gradients. Nat. Commun. 16, 6765 (2025).","journal-title":"Nat. Commun."},{"key":"10281_CR28","doi-asserted-by":"publisher","DOI":"10.1002\/0471142735.im1912s55","author":"M Camberis","year":"2003","unstructured":"Camberis, M., Le Gros, G. & Urban, J. Animal model of Nippostrongylus brasiliensis and Heligmosomoides polygyrus. Curr. Protoc. Immunol. https:\/\/doi.org\/10.1002\/0471142735.im1912s55 (2003).","journal-title":"Curr. Protoc. Immunol."},{"key":"10281_CR29","doi-asserted-by":"publisher","first-page":"9478","DOI":"10.1073\/pnas.1019418108","volume":"108","author":"G Krasteva","year":"2011","unstructured":"Krasteva, G. et al. Cholinergic chemosensory cells in the trachea regulate breathing. Proc. Natl Acad. Sci. USA 108, 9478\u20139483 (2011).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"10281_CR30","doi-asserted-by":"publisher","first-page":"878","DOI":"10.1038\/s41586-022-04515-5","volume":"603","author":"Q Zhao","year":"2022","unstructured":"Zhao, Q. et al. A multidimensional coding architecture of the vagal interoceptive system. Nature 603, 878\u2013884 (2022).","journal-title":"Nature"},{"key":"10281_CR31","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11905","volume":"7","author":"CW Roman","year":"2016","unstructured":"Roman, C. W., Derkach, V. A. & Palmiter, R. D. Genetically and functionally defined NTS to PBN brain circuits mediating anorexia. Nat. Commun. 7, 11905 (2016).","journal-title":"Nat. Commun."},{"key":"10281_CR32","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1016\/j.cmet.2019.11.016","volume":"31","author":"I Aklan","year":"2020","unstructured":"Aklan, I. et al. NTS catecholamine neurons mediate hypoglycemic hunger via medial hypothalamic feeding pathways. Cell Metab. 31, 313\u2013326.e315 (2020).","journal-title":"Cell Metab."},{"key":"10281_CR33","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1038\/s41586-023-06758-2","volume":"624","author":"T Ly","year":"2023","unstructured":"Ly, T. et al. Sequential appetite suppression by oral and visceral feedback to the brainstem. Nature 624, 130\u2013137 (2023).","journal-title":"Nature"},{"key":"10281_CR34","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1038\/s41586-024-07608-5","volume":"631","author":"Y Su","year":"2024","unstructured":"Su, Y. et al. Brainstem Dbh+ neurons control allergen-induced airway hyperreactivity. Nature 631, 601\u2013609 (2024).","journal-title":"Nature"},{"key":"10281_CR35","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.74964","volume":"11","author":"L Bai","year":"2022","unstructured":"Bai, L. et al. Enteroendocrine cell types that drive food reward and aversion. eLife 11, e74964 (2022).","journal-title":"eLife"},{"key":"10281_CR36","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.jneumeth.2013.12.010","volume":"224","author":"J Brodkin","year":"2014","unstructured":"Brodkin, J. et al. Validation and implementation of a novel high-throughput behavioral phenotyping instrument for mice. J. Neurosci. Methods 224, 48\u201357 (2014).","journal-title":"J. Neurosci. Methods"},{"key":"10281_CR37","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1126\/science.adz1398","volume":"390","author":"A Venkataraman","year":"2025","unstructured":"Venkataraman, A. et al. A cellular basis for heightened gut sensitivity in females. Science 390, 1285\u20131291 (2025).","journal-title":"Science"},{"key":"10281_CR38","doi-asserted-by":"publisher","first-page":"1581","DOI":"10.1084\/jem.20161807","volume":"214","author":"S Laffont","year":"2017","unstructured":"Laffont, S. et al. Androgen signaling negatively controls group 2 innate lymphoid cells. J. Exp. Med. 214, 1581\u20131592 (2017).","journal-title":"J. Exp. Med."},{"key":"10281_CR39","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1038\/mi.2017.20","volume":"11","author":"C Su","year":"2018","unstructured":"Su, C. et al. Helminth-induced alterations of the gut microbiota exacerbate bacterial colitis. Mucosal Immunol 11, 144\u2013157 (2018).","journal-title":"Mucosal Immunol"},{"key":"10281_CR40","doi-asserted-by":"publisher","first-page":"2135","DOI":"10.3389\/fimmu.2018.02135","volume":"9","author":"GS Yap","year":"2018","unstructured":"Yap, G. S. & Gause, W. C. Helminth infections induce tissue tolerance mitigating immunopathology but enhancing microbial pathogen susceptibility. Front. Immunol. 9, 2135 (2018).","journal-title":"Front. Immunol."},{"key":"10281_CR41","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1016\/j.immuni.2025.01.004","volume":"58","author":"Y Wang","year":"2025","unstructured":"Wang, Y. et al. Bi-directional communication between intrinsic enteric neurons and ILC2s inhibits host defense against helminth infection. Immunity 58, 465\u2013480 (2025).","journal-title":"Immunity"},{"key":"10281_CR42","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1038\/nature23469","volume":"549","author":"V Cardoso","year":"2017","unstructured":"Cardoso, V. et al. Neuronal regulation of type 2 innate lymphoid cells via neuromedin U. Nature 549, 277\u2013281 (2017).","journal-title":"Nature"},{"key":"10281_CR43","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1126\/science.adn9850","volume":"389","author":"RM Barilla","year":"2025","unstructured":"Barilla, R. M. et al. Type 2 cytokines act on enteric sensory neurons to regulate neuropeptide-driven host defense. Science 389, 260\u2013267 (2025).","journal-title":"Science"},{"key":"10281_CR44","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1128\/CMR.05040-11","volume":"25","author":"HJ McSorley","year":"2012","unstructured":"McSorley, H. J. & Maizels, R. M. Helminth infections and host immune regulation. Clin. Microbiol. Rev. 25, 585\u2013608 (2012).","journal-title":"Clin. Microbiol. Rev."},{"key":"10281_CR45","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2024.102963","volume":"90","author":"C Zhang","year":"2025","unstructured":"Zhang, C. Neural pathways of nausea and roles in energy balance. Curr. Opin. Neurobiol. 90, 102963 (2025).","journal-title":"Curr. Opin. Neurobiol."},{"key":"10281_CR46","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1053\/j.gastro.2024.01.045","volume":"166","author":"AC Ford","year":"2024","unstructured":"Ford, A. C., Vanner, S., Kashyap, P. C. & Nasser, Y. Chronic visceral pain: new peripheral mechanistic insights and resulting treatments. Gastroenterology 166, 976\u2013994 (2024).","journal-title":"Gastroenterology"},{"key":"10281_CR47","doi-asserted-by":"publisher","first-page":"2203","DOI":"10.1016\/j.cell.2025.03.006","volume":"188","author":"Y Lee","year":"2025","unstructured":"Lee, Y. et al. Brain-wide mapping of immune receptors uncovers a neuromodulatory role of IL-17E and the receptor IL-17RB. Cell 188, 2203\u20132217 (2025).","journal-title":"Cell"},{"key":"10281_CR48","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1016\/j.immuni.2020.03.005","volume":"52","author":"A Perniss","year":"2020","unstructured":"Perniss, A. et al. Chemosensory cell-derived acetylcholine drives tracheal mucociliary clearance in response to virulence-associated formyl peptides. Immunity 52, 683\u2013699 (2020).","journal-title":"Immunity"},{"key":"10281_CR49","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.intimp.2015.05.028","volume":"29","author":"G Krasteva-Christ","year":"2015","unstructured":"Krasteva-Christ, G. et al. Identification of cholinergic chemosensory cells in mouse tracheal and laryngeal glandular ducts. Int. Immunopharmacol. 29, 158\u2013165 (2015).","journal-title":"Int. Immunopharmacol."},{"key":"10281_CR50","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abf6734","volume":"7","author":"M Keshavarz","year":"2022","unstructured":"Keshavarz, M. et al. Cysteinyl leukotrienes and acetylcholine are biliary tuft cell cotransmitters. Sci. Immunol. 7, eabf6734 (2022).","journal-title":"Sci. Immunol."},{"key":"10281_CR51","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1038\/nature07935","volume":"459","author":"T Sato","year":"2009","unstructured":"Sato, T. et al. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 459, 262\u2013265 (2009).","journal-title":"Nature"},{"key":"10281_CR52","doi-asserted-by":"publisher","DOI":"10.1002\/0471142727.mb1420s92","author":"Arthur Edelstein","year":"2010","unstructured":"Edelstein, A., Amodaj, N., Hoover, K., Vale, R. & Stuurman, N. Computer control of microscopes using \u00b5Manager. Curr. Protoc. Mol. Biol. https:\/\/doi.org\/10.1002\/0471142727.mb1420s92 (2010).","journal-title":"Curr. Protoc. Mol. Biol."},{"key":"10281_CR53","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1038\/ni.2182","volume":"13","author":"HE Liang","year":"2011","unstructured":"Liang, H. E. et al. Divergent expression patterns of IL-4 and IL-13 define unique functions in allergic immunity. Nat. Immunol. 13, 58\u201366 (2011).","journal-title":"Nat. Immunol."},{"key":"10281_CR54","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202002441R","volume":"35","author":"J Castro","year":"2021","unstructured":"Castro, J. et al. A mouse model of endometriosis that displays vaginal, colon, cutaneous, and bladder sensory comorbidities. FASEB J. 35, e21430 (2021).","journal-title":"FASEB J."},{"key":"10281_CR55","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1038\/nprot.2006.170","volume":"1","author":"RM Deacon","year":"2006","unstructured":"Deacon, R. M. Assessing nest building in mice. Nat. Protoc. 1, 1117\u20131119 (2006).","journal-title":"Nat. Protoc."},{"key":"10281_CR56","doi-asserted-by":"publisher","first-page":"451","DOI":"10.30802\/AALAS-CM-19-000042","volume":"69","author":"PV Turner","year":"2019","unstructured":"Turner, P. V., Pang, D. S. & Lofgren, J. L. A review of pain assessment methods in laboratory rodents. Comp. Med. 69, 451\u2013467 (2019).","journal-title":"Comp. Med."}],"container-title":["Nature"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41586-026-10281-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41586-026-10281-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41586-026-10281-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T23:12:47Z","timestamp":1778713967000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41586-026-10281-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,25]]},"references-count":56,"journal-issue":{"issue":"8114","published-print":{"date-parts":[[2026,5,14]]}},"alternative-id":["10281"],"URL":"https:\/\/doi.org\/10.1038\/s41586-026-10281-5","relation":{},"ISSN":["0028-0836","1476-4687"],"issn-type":[{"value":"0028-0836","type":"print"},{"value":"1476-4687","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,25]]},"assertion":[{"value":"16 April 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}