{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T00:19:28Z","timestamp":1792196368450,"version":"4.4.0"},"reference-count":85,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,1,9]],"date-time":"2021-01-09T00:00:00Z","timestamp":1610150400000},"content-version":"vor","delay-in-days":374,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100011684","name":"Crohn&apos;s and Colitis Foundation","doi-asserted-by":"publisher","award":["569103"],"award-info":[{"award-number":["569103"]}],"id":[{"id":"10.13039\/100011684","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01GM131642A"],"award-info":[{"award-number":["R01GM131642A"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01GM135928"],"award-info":[{"award-number":["R01GM135928"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HG008383"],"award-info":[{"award-number":["R01HG008383"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["91715377"],"award-info":[{"award-number":["91715377"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004330","name":"GlaxoSmithKline","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011643","name":"Blavatnik Family Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011643","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001063","name":"Crohn&apos;s and Colitis Foundation of America","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001063","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001829","name":"Universiteit Utrecht","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001829","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["320030_182764"],"award-info":[{"award-number":["320030_182764"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["Fall 2007 DGE1752134"],"award-info":[{"award-number":["Fall 2007 DGE1752134"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008328","name":"Marshallplan-Jubil\u00e4umsstiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008328","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Cell"],"published-print":{"date-parts":[[2020,1]]},"DOI":"10.1016\/j.cell.2019.12.016","type":"journal-article","created":{"date-parts":[[2020,1,9]],"date-time":"2020-01-09T10:38:13Z","timestamp":1578566293000},"page":"50-63.e12","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":174,"title":["Enteric Nervous System-Derived IL-18 Orchestrates Mucosal Barrier Immunity"],"prefix":"10.1016","volume":"180","author":[{"given":"Abigail","family":"Jarret","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruaidhr\u00ed","family":"Jackson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Coco","family":"Duizer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc E.","family":"Healy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph M.","family":"Rone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Bielecki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esen","family":"Sefik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manolis","family":"Roulis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler","family":"Rice","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kisha N.","family":"Sivanathan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angel G.","family":"Solis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Honcharova-Biletska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karelia","family":"V\u00e9lez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saskia","family":"Hartner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun Siong","family":"Low","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rihao","family":"Qu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel R.","family":"de Zoete","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noah W.","family":"Palm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron M.","family":"Ring","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achim","family":"Weber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas E.","family":"Moor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuval","family":"Kluger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roni","family":"Nowarski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Flavell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.cell.2019.12.016_bib1","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1053\/j.sempedsurg.2012.07.006","article-title":"The pathogenesis of Hirschsprung\u2019s disease-associated enterocolitis","volume":"21","author":"Austin","year":"2012","journal-title":"Semin. Pediatr. Surg."},{"key":"10.1016\/j.cell.2019.12.016_bib2","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1084\/jem.20140654","article-title":"NOS1-derived nitric oxide promotes NF-\u03baB transcriptional activity through inhibition of suppressor of cytokine signaling-1","volume":"212","author":"Baig","year":"2015","journal-title":"J.\u00a0Exp. Med."},{"key":"10.1016\/j.cell.2019.12.016_bib3","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1369\/jhc.2009.953539","article-title":"Toll-like receptors 3, 4, and 7 are expressed in the enteric nervous system and dorsal root ganglia","volume":"57","author":"Barajon","year":"2009","journal-title":"J.\u00a0Histochem. Cytochem."},{"key":"10.1016\/j.cell.2019.12.016_bib4","doi-asserted-by":"crossref","first-page":"2839","DOI":"10.1128\/IAI.71.5.2839-2858.2003","article-title":"Pretreatment of mice with streptomycin provides a Salmonella enterica serovar Typhimurium colitis model that allows analysis of both pathogen and host","volume":"71","author":"Barthel","year":"2003","journal-title":"Infect. Immun."},{"key":"10.1016\/j.cell.2019.12.016_bib5","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1111\/nmo.12015","article-title":"Nestin-expressing cells in the gut give rise to enteric neurons and glial cells","volume":"25","author":"Belkind-Gerson","year":"2013","journal-title":"Neurogastroenterol. Motil."},{"key":"10.1016\/j.cell.2019.12.016_bib6","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1126\/science.aaf7419","article-title":"A sentinel goblet cell guards the colonic crypt by triggering Nlrp6-dependent Muc2 secretion","volume":"352","author":"Birchenough","year":"2016","journal-title":"Science"},{"key":"10.1016\/j.cell.2019.12.016_bib7","doi-asserted-by":"crossref","first-page":"E2003","DOI":"10.3390\/ijms20082003","article-title":"Nitrergic Enteric Neurons in Health and Disease-Focus on Animal Models","volume":"20","author":"B\u00f3di","year":"2019","journal-title":"Int J Mol Sci."},{"key":"10.1016\/j.cell.2019.12.016_bib8","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1038\/nature11419","article-title":"Caspase-11 increases susceptibility to Salmonella infection in the absence of caspase-1","volume":"490","author":"Broz","year":"2012","journal-title":"Nature"},{"key":"10.1016\/j.cell.2019.12.016_bib84","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/nbt.4096","article-title":"Integrating single-cell transcriptomic data across different conditions, technologies, and species","volume":"36","author":"Butler","year":"2018","journal-title":"Nat Biotechnol."},{"key":"10.1016\/j.cell.2019.12.016_bib9","first-page":"801","volume":"135","author":"Caccamo","year":"1989","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.cell.2019.12.016_bib10","first-page":"17","article-title":"Interactions of intestinal epithelial cells with bacteria and immune cells: methods to characterize microflora and functional consequences","volume":"341","author":"Canny","year":"2006","journal-title":"Methods Mol. Biol."},{"key":"10.1016\/j.cell.2019.12.016_bib11","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1073\/pnas.1211521110","article-title":"Caspase-11 stimulates rapid flagellin-independent pyroptosis in response to Legionella pneumophila","volume":"110","author":"Case","year":"2013","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.cell.2019.12.016_bib82","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1046\/j.1365-2958.1996.471410.x","article-title":"Salmonella spp. are cytotoxic for cultured macrophages","volume":"21","author":"Chen","year":"1996","journal-title":"Mol Microbiol."},{"key":"10.1016\/j.cell.2019.12.016_bib12","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1097\/shk.0b013e31805569df","article-title":"Intestinal crosstalk: a new paradigm for understanding the gut as the \u201cmotor\u201d of critical illness","volume":"28","author":"Clark","year":"2007","journal-title":"Shock"},{"key":"10.1016\/j.cell.2019.12.016_bib13","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1186\/s12974-014-0202-7","article-title":"Modulation of lipopolysaccharide-induced neuronal response by activation of the enteric nervous system","volume":"11","author":"Coquenlorge","year":"2014","journal-title":"J.\u00a0Neuroinflammation"},{"key":"10.1016\/j.cell.2019.12.016_bib14","doi-asserted-by":"crossref","first-page":"2237","DOI":"10.1242\/dev.003814","article-title":"Hand2 is necessary for terminal differentiation of enteric neurons from crest-derived precursors but not for their migration into the gut or for formation of glia","volume":"134","author":"D\u2019Autr\u00e9aux","year":"2007","journal-title":"Development"},{"key":"10.1016\/j.cell.2019.12.016_bib15","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1146\/annurev.immunol.021908.132612","article-title":"Immunological and inflammatory functions of the interleukin-1 family","volume":"27","author":"Dinarello","year":"2009","journal-title":"Annu. Rev. Immunol."},{"key":"10.1016\/j.cell.2019.12.016_bib16","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1002\/gene.10154","article-title":"Inducible site-specific recombination in myelinating cells","volume":"35","author":"Doerflinger","year":"2003","journal-title":"Genesis"},{"key":"10.1016\/j.cell.2019.12.016_bib17","article-title":"The enteric nervous system of the human and mouse colon at a single-cell resolution","author":"Drokhlyansky","year":"2019","journal-title":"bioRxiv"},{"key":"10.1016\/j.cell.2019.12.016_bib18","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/j.cell.2011.04.022","article-title":"NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis","volume":"145","author":"Elinav","year":"2011","journal-title":"Cell"},{"key":"10.1016\/j.cell.2019.12.016_bib19","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1038\/ni.2913","article-title":"The adaptor ASC has extracellular and \u2018prionoid\u2019 activities that propagate inflammation","volume":"15","author":"Franklin","year":"2014","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.cell.2019.12.016_bib20","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/978-1-4939-0897-4_3","article-title":"The enteric nervous system and gastrointestinal innervation: integrated local and central control","volume":"817","author":"Furness","year":"2014","journal-title":"Adv. Exp. Med. Biol."},{"key":"10.1016\/j.cell.2019.12.016_bib21","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.cell.2015.12.023","article-title":"Neuro-immune Interactions Drive Tissue Programming in Intestinal Macrophages","volume":"164","author":"Gabanyi","year":"2016","journal-title":"Cell"},{"key":"10.1016\/j.cell.2019.12.016_bib22","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1016\/j.cell.2017.01.022","article-title":"Mining the Human Gut Microbiota for Immunomodulatory Organisms","volume":"168","author":"Geva-Zatorsky","year":"2017","journal-title":"Cell"},{"key":"10.1016\/j.cell.2019.12.016_bib23","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1126\/science.275.5297.206","article-title":"Activation of Interferon-\u03b3 Inducing Factor Mediated by Interleukin-1\u03b2 Converting Enzyme","volume":"275","author":"Gu","year":"1997","journal-title":"Science"},{"key":"10.1016\/j.cell.2019.12.016_bib24","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.mib.2011.11.002","article-title":"Role of mucus layers in gut infection and inflammation","volume":"15","author":"Hansson","year":"2012","journal-title":"Curr. Opin. Microbiol."},{"key":"10.1016\/j.cell.2019.12.016_bib25","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1038\/cr.2015.139","article-title":"Gasdermin D is an executor of pyroptosis and required for interleukin-1\u03b2 secretion","volume":"25","author":"He","year":"2015","journal-title":"Cell Res."},{"key":"10.1016\/j.cell.2019.12.016_bib26","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1002\/dvdy.20989","article-title":"Expression of Hand2 is sufficient for neurogenesis and cell type-specific gene expression in the enteric nervous system","volume":"236","author":"Hendershot","year":"2007","journal-title":"Dev. Dyn."},{"key":"10.1016\/j.cell.2019.12.016_bib27","first-page":"1","article-title":"Stuhtragheit Neugeborener infolge Dilatationen und hypertrophie des Colons","volume":"27","author":"Hirschsprung","year":"1887","journal-title":"Jahruch Kinderheikunde"},{"key":"10.1016\/j.cell.2019.12.016_bib28","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1136\/gutjnl-2017-315631","article-title":"Single-cell RNAseq reveals seven classes of colonic sensory neuron","volume":"68","author":"Hockley","year":"2019","journal-title":"Gut"},{"key":"10.1016\/j.cell.2019.12.016_bib29","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/nri2710","article-title":"Immune adaptations that maintain homeostasis with the intestinal microbiota","volume":"10","author":"Hooper","year":"2010","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.cell.2019.12.016_bib30","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/s41586-018-0794-7","article-title":"The translation of non-canonical open reading frames controls mucosal immunity","volume":"564","author":"Jackson","year":"2018","journal-title":"Nature"},{"key":"10.1016\/j.cell.2019.12.016_bib85","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1038\/nm.4211","article-title":"Hepatitis-C-virus-induced microRNAs dampen interferon-mediated antiviral signaling","volume":"22","author":"Jarret","year":"2016","journal-title":"Nat Med."},{"key":"10.1016\/j.cell.2019.12.016_bib31","doi-asserted-by":"crossref","first-page":"3398","DOI":"10.1172\/JCI58186","article-title":"Enteric glia are multipotent in culture but primarily form glia in the adult rodent gut","volume":"121","author":"Joseph","year":"2011","journal-title":"J.\u00a0Clin. Invest."},{"key":"10.1016\/j.cell.2019.12.016_bib32","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.1053\/gast.2000.20260","article-title":"Interleukin 18 is a potent proliferative factor for intestinal mucosal lymphocytes in Crohn\u2019s disease","volume":"119","author":"Kanai","year":"2000","journal-title":"Gastroenterology"},{"key":"10.1016\/j.cell.2019.12.016_bib33","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/nature10558","article-title":"Non-canonical inflammasome activation targets caspase-11","volume":"479","author":"Kayagaki","year":"2011","journal-title":"Nature"},{"key":"10.1016\/j.cell.2019.12.016_bib34","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/nature15541","article-title":"Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling","volume":"526","author":"Kayagaki","year":"2015","journal-title":"Nature"},{"key":"10.1016\/j.cell.2019.12.016_bib35","doi-asserted-by":"crossref","first-page":"2686","DOI":"10.4049\/jimmunol.1501162","article-title":"Nestin-Expressing Precursors Give Rise to Both Endothelial as well as Nonendothelial Lymph Node Stromal Cells","volume":"197","author":"Koning","year":"2016","journal-title":"J Immunol."},{"key":"10.1016\/j.cell.2019.12.016_bib36","doi-asserted-by":"crossref","first-page":"5112","DOI":"10.1128\/AEM.01043-13","article-title":"Development of a Dual-Index Sequencing Strategy and Curation Pipeline for Analyzing Amplicon Sequence Data on the MiSeq Illumina Sequencing Platform","volume":"79","author":"Kozich","year":"2013","journal-title":"Appl Environ Microbiol."},{"key":"10.1016\/j.cell.2019.12.016_bib37","doi-asserted-by":"crossref","first-page":"E3709","DOI":"10.1073\/pnas.1619406114","article-title":"Adult enteric nervous system in health is maintained by a dynamic balance between neuronal apoptosis and neurogenesis","volume":"114","author":"Kulkarni","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.cell.2019.12.016_bib38","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.neulet.2017.03.051","article-title":"Interleukin-18 and its receptor are expressed in gonadotropin-releasing\u00a0hormone neurons of mouse and rat forebrain","volume":"650","author":"Kuwahara-Otani","year":"2017","journal-title":"Neurosci. Lett."},{"key":"10.1016\/j.cell.2019.12.016_bib39","doi-asserted-by":"crossref","first-page":"12623","DOI":"10.1523\/JNEUROSCI.3812-07.2007","article-title":"Dynamic contribution of nestin-expressing stem cells to adult neurogenesis","volume":"27","author":"Lagace","year":"2007","journal-title":"J.\u00a0Neurosci."},{"key":"10.1016\/j.cell.2019.12.016_bib40","article-title":"Gut-innervating nociceptor neurons protect against enteric infection by modulating the microbiota and Peyer\u2019s patch microfold cells","author":"Lai","year":"2019","journal-title":"bioRxiv"},{"key":"10.1016\/j.cell.2019.12.016_bib41","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1084\/jem.20060206","article-title":"Role of the caspase-1 inflammasome in Salmonella typhimurium pathogenesis","volume":"203","author":"Lara-Tejero","year":"2006","journal-title":"J.\u00a0Exp. Med."},{"key":"10.1016\/j.cell.2019.12.016_bib42","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1016\/j.cell.2015.10.048","article-title":"Microbiota-Modulated Metabolites Shape the Intestinal Microenvironment by Regulating NLRP6 Inflammasome Signaling","volume":"163","author":"Levy","year":"2015","journal-title":"Cell"},{"key":"10.1016\/j.cell.2019.12.016_bib43","article-title":"Zero-preserving imputation of scRNA-seq data using low-rank approximation","author":"Linderman","year":"2018","journal-title":"bioRxiv"},{"key":"10.1016\/j.cell.2019.12.016_bib83","first-page":"2579","article-title":"Visualizing Data using t-SNE","volume":"9","author":"Maaten","year":"2008","journal-title":"J Mach Learn Res."},{"key":"10.1016\/j.cell.2019.12.016_bib44","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1016\/j.cell.2015.05.002","article-title":"Highly Parallel Genome-wide Expression Profiling of Individual Cells Using Nanoliter Droplets","volume":"161","author":"Macosko","year":"2015","journal-title":"Cell"},{"key":"10.1016\/j.cell.2019.12.016_bib45","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/nn.2467","article-title":"A robust and high-throughput Cre reporting and characterization system for the whole mouse brain","volume":"13","author":"Madisen","year":"2010","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.cell.2019.12.016_bib46","doi-asserted-by":"crossref","first-page":"33275","DOI":"10.1074\/jbc.M204935200","article-title":"Cis elements of the villin gene control expression in restricted domains of the vertical (crypt) and horizontal (duodenum, cecum) axes of the intestine","volume":"277","author":"Madison","year":"2002","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.cell.2019.12.016_bib47","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/S1097-2765(02)00599-3","article-title":"The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta","volume":"10","author":"Martinon","year":"2002","journal-title":"Mol. Cell"},{"key":"10.1016\/j.cell.2019.12.016_bib86","doi-asserted-by":"crossref","DOI":"10.1016\/j.cell.2019.12.002","article-title":"Adrenergic Signaling in Muscularis Macrophages Limits Infection-Induced Neuronal Loss","volume":"180","author":"Matheis","year":"2020","journal-title":"Cell"},{"key":"10.1016\/j.cell.2019.12.016_bib49","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1111\/j.1365-2249.2006.03159.x","article-title":"A potential role for interleukin-18 in inhibition of the development of Cryptosporidium parvum","volume":"145","author":"McDonald","year":"2006","journal-title":"Clin. Exp. Immunol."},{"key":"10.1016\/j.cell.2019.12.016_bib50","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1038\/nature09262","article-title":"Mesenchymal and haematopoietic stem cells form a unique bone marrow niche","volume":"466","author":"M\u00e9ndez-Ferrer","year":"2010","journal-title":"Nature"},{"key":"10.1016\/j.cell.2019.12.016_bib51","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1016\/j.celrep.2018.07.027","article-title":"Interleukin-1\u03b2 Maturation Triggers Its Relocation to the Plasma Membrane for Gasdermin-D-Dependent and -Independent Secretion","volume":"24","author":"Monteleone","year":"2018","journal-title":"Cell Rep."},{"key":"10.1016\/j.cell.2019.12.016_bib52","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1016\/j.cell.2018.08.063","article-title":"Spatial Reconstruction of Single Enterocytes Uncovers Broad Zonation along the Intestinal Villus Axis","volume":"175","author":"Moor","year":"2018","journal-title":"Cell"},{"key":"10.1016\/j.cell.2019.12.016_bib53","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1002\/gene.10175","article-title":"Evidence for novel fate of Flk1+ progenitor: contribution to muscle lineage","volume":"35","author":"Motoike","year":"2003","journal-title":"Genesis"},{"key":"10.1016\/j.cell.2019.12.016_bib54","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1016\/j.cell.2015.10.072","article-title":"Epithelial IL-18 Equilibrium Controls Barrier Function in Colitis","volume":"163","author":"Nowarski","year":"2015","journal-title":"Cell"},{"key":"10.1016\/j.cell.2019.12.016_bib55","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/S0022-3468(67)80085-X","article-title":"Embryogenesis of intramural ganglia of the gut and its relation to Hirschsprung\u2019s disease","volume":"2","author":"Okamoto","year":"1967","journal-title":"J.\u00a0Pediatr. Surg."},{"key":"10.1016\/j.cell.2019.12.016_bib56","doi-asserted-by":"crossref","first-page":"8315","DOI":"10.4049\/jimmunol.177.12.8315","article-title":"Human mast cell chymase cleaves pro-IL-18 and generates a novel and biologically active IL-18 fragment","volume":"177","author":"Omoto","year":"2006","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.cell.2019.12.016_bib57","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.jdermsci.2010.05.004","article-title":"Granzyme B is a novel interleukin-18 converting enzyme","volume":"59","author":"Omoto","year":"2010","journal-title":"J.\u00a0Dermatol. Sci."},{"key":"10.1016\/j.cell.2019.12.016_bib58","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1016\/j.cell.2014.08.006","article-title":"Immunoglobulin A coating identifies colitogenic bacteria in inflammatory bowel disease","volume":"158","author":"Palm","year":"2014","journal-title":"Cell"},{"key":"10.1016\/j.cell.2019.12.016_bib59","doi-asserted-by":"crossref","first-page":"11027","DOI":"10.1073\/pnas.1711395114","article-title":"Resistin-like molecule \u03b2 is a bactericidal protein that promotes spatial segregation of the microbiota and the colonic epithelium","volume":"114","author":"Propheter","year":"2017","journal-title":"Proc Natl Acad Sci USA."},{"key":"10.1016\/j.cell.2019.12.016_bib60","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/s00441-008-0684-7","article-title":"Immunohistochemical analysis of neuron types in the mouse small intestine","volume":"334","author":"Qu","year":"2008","journal-title":"Cell Tissue Res."},{"key":"10.1016\/j.cell.2019.12.016_bib61","doi-asserted-by":"crossref","first-page":"2040","DOI":"10.1002\/glia.22876","article-title":"Enteric glia express proteolipid protein 1 and are a transcriptionally unique population of glia in the mammalian nervous system","volume":"63","author":"Rao","year":"2015","journal-title":"Glia"},{"key":"10.1016\/j.cell.2019.12.016_bib62","doi-asserted-by":"crossref","first-page":"4922","DOI":"10.1128\/IAI.00417-06","article-title":"Caspase-1-mediated activation of interleukin-1\u03b2 (IL-1\u03b2) and IL-18 contributes to innate immune defenses against Salmonella enterica serovar Typhimurium infection","volume":"74","author":"Raupach","year":"2006","journal-title":"Infect. Immun."},{"key":"10.1016\/j.cell.2019.12.016_bib63","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/S0012-1606(03)00068-X","article-title":"dHAND-Cre transgenic mice reveal specific potential functions of dHAND during craniofacial development","volume":"257","author":"Ruest","year":"2003","journal-title":"Dev. Biol."},{"key":"10.1016\/j.cell.2019.12.016_bib64","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/BF00319611","article-title":"Bethanechol and a G-protein activator, NaF\/AlCl3, induce secretory response in Paneth cells of mouse intestine","volume":"269","author":"Satoh","year":"1992","journal-title":"Cell Tissue Res."},{"key":"10.1016\/j.cell.2019.12.016_bib65","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1053\/j.gastro.2013.01.040","article-title":"Functions and imaging of mast cell and neural axis of the gut","volume":"144","author":"Schemann","year":"2013","journal-title":"Gastroenterology"},{"key":"10.1016\/j.cell.2019.12.016_bib66","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1126\/science.aaa9420","article-title":"Individual intestinal symbionts induce a distinct population of ROR\u03b3+ regulatory T cells","volume":"349","author":"Sefik","year":"2015","journal-title":"Science"},{"key":"10.1016\/j.cell.2019.12.016_bib67","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/0092-8674(94)90150-3","article-title":"Glial growth factor restricts mammalian neural crest stem cells to a glial fate","volume":"77","author":"Shah","year":"1994","journal-title":"Cell"},{"key":"10.1016\/j.cell.2019.12.016_bib68","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1016\/j.cell.2016.07.054","article-title":"Comprehensive Classification of Retinal Bipolar Neurons by Single-Cell Transcriptomics","volume":"166","author":"Shekhar","year":"2016","journal-title":"Cell"},{"key":"10.1016\/j.cell.2019.12.016_bib69","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1038\/nature15514","article-title":"Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death","volume":"526","author":"Shi","year":"2015","journal-title":"Nature"},{"key":"10.1016\/j.cell.2019.12.016_bib70","doi-asserted-by":"crossref","DOI":"10.3791\/50688-v","article-title":"An in-vitro preparation of isolated enteric neurons and glia from the myenteric plexus of the adult mouse","author":"Smith","year":"2013","journal-title":"J.\u00a0Vis. Exp."},{"key":"10.1016\/j.cell.2019.12.016_bib71","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.1136\/gut.2006.091322","article-title":"The role of the sympathetic nervous system in intestinal inflammation","volume":"55","author":"Straub","year":"2006","journal-title":"Gut."},{"key":"10.1016\/j.cell.2019.12.016_bib72","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1038\/nature10759","article-title":"Inflammasomes in health and disease","volume":"481","author":"Strowig","year":"2012","journal-title":"Nature"},{"key":"10.1016\/j.cell.2019.12.016_bib73","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0006-8993(02)03363-2","article-title":"Neurons of the superior nucleus of the medial habenula and ependymal cells express IL-18 in rat CNS","volume":"958","author":"Sugama","year":"2002","journal-title":"Brain Res."},{"key":"10.1016\/j.cell.2019.12.016_bib74","article-title":"VIP-producing enteric neurons interact with innate lymphoid cells to regulate feeding-dependent intestinal epithelial barrier functions","author":"Talbot","year":"2019","journal-title":"bioRxiv"},{"key":"10.1016\/j.cell.2019.12.016_bib75","doi-asserted-by":"crossref","first-page":"e99944","DOI":"10.1371\/journal.pone.0099944","article-title":"Altered goblet cell differentiation and surface mucus properties in Hirschsprung disease","volume":"9","author":"Thiagarajah","year":"2014","journal-title":"PLoS ONE"},{"key":"10.1016\/j.cell.2019.12.016_bib76","doi-asserted-by":"crossref","DOI":"10.3791\/55347","article-title":"The Ex\u00a0Vivo Colon Organ Culture and Its Use in Antimicrobial Host Defense Studies","author":"Udden","year":"2017","journal-title":"J.\u00a0Vis. Exp."},{"key":"10.1016\/j.cell.2019.12.016_bib77","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1126\/science.aal3589","article-title":"Astrocyte-derived interleukin-33 promotes microglial synapse engulfment and neural circuit development","volume":"359","author":"Vainchtein","year":"2018","journal-title":"Science"},{"key":"10.1016\/j.cell.2019.12.016_bib78","doi-asserted-by":"crossref","first-page":"2510","DOI":"10.1007\/s00018-004-4144-6","article-title":"Nestin expression--a property of multi-lineage progenitor cells?","volume":"61","author":"Wiese","year":"2004","journal-title":"Cell. Mol. Life Sci."},{"key":"10.1016\/j.cell.2019.12.016_bib79","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1016\/j.immuni.2017.05.011","article-title":"The Enteric Network: Interactions between the Immune and Nervous Systems of the Gut","volume":"46","author":"Yoo","year":"2017","journal-title":"Immunity"},{"key":"10.1016\/j.cell.2019.12.016_bib80","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1016\/j.cell.2018.06.021","article-title":"Molecular Architecture of the Mouse Nervous System","volume":"174","author":"Zeisel","year":"2018","journal-title":"Cell"},{"key":"10.1016\/j.cell.2019.12.016_bib81","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1038\/nprot.2006.142","article-title":"Isolation of DNA from bacterial samples of the human gastrointestinal tract","volume":"1","author":"Zoetendal","year":"2006","journal-title":"Nat. Protoc."}],"updated-by":[{"DOI":"10.1016\/j.cell.2020.02.004","type":"erratum","label":"Erratum","source":"publisher","updated":{"date-parts":[[2020,2,20]],"date-time":"2020-02-20T00:00:00Z","timestamp":1582156800000}}],"container-title":["Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0092867419313789?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0092867419313789?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T15:11:57Z","timestamp":1777475517000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0092867419313789"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1]]},"references-count":85,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,1]]}},"alternative-id":["S0092867419313789"],"URL":"https:\/\/doi.org\/10.1016\/j.cell.2019.12.016","relation":{},"ISSN":["0092-8674"],"issn-type":[{"value":"0092-8674","type":"print"}],"subject":[],"published":{"date-parts":[[2020,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Enteric Nervous System-Derived IL-18 Orchestrates Mucosal Barrier Immunity","name":"articletitle","label":"Article Title"},{"value":"Cell","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.cell.2019.12.016","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"https:\/\/doi.org\/10.1016\/j.cell.2019.11.014","name":"associatedlink","label":"CrossRef DOI link to the associated document"},{"value":"https:\/\/doi.org\/10.1016\/j.cell.2019.12.002","name":"associatedlink","label":"CrossRef DOI link to the associated document"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 Elsevier Inc.","name":"copyright","label":"Copyright"}]}}