{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T15:13:40Z","timestamp":1793373220985,"version":"4.5.0"},"reference-count":151,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T00:00:00Z","timestamp":1750204800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T00:00:00Z","timestamp":1750204800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Rev Gastroenterol Hepatol"],"published-print":{"date-parts":[[2025,9]]},"DOI":"10.1038\/s41575-025-01086-4","type":"journal-article","created":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T11:47:47Z","timestamp":1750247267000},"page":"657-667","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["The oesophagus as an immune organ"],"prefix":"10.1038","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0818-927X","authenticated-orcid":false,"given":"Mark","family":"Rochman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kendall","family":"Kellerman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4700-096X","authenticated-orcid":false,"given":"Michael P.","family":"Jankowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9790-6332","authenticated-orcid":false,"given":"Marc E.","family":"Rothenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,18]]},"reference":[{"key":"1086_CR1","doi-asserted-by":"publisher","first-page":"1244","DOI":"10.1038\/ng.2739","volume":"45","author":"L Samuelov","year":"2013","unstructured":"Samuelov, L. et al. Desmoglein 1 deficiency results in severe dermatitis, multiple allergies and metabolic wasting. Nat. Genet. 45, 1244\u20131248 (2013).","journal-title":"Nat. Genet."},{"key":"1086_CR2","doi-asserted-by":"publisher","first-page":"195ra194","DOI":"10.1126\/scitranslmed.3006448","volume":"5","author":"PA Frischmeyer-Guerrerio","year":"2013","unstructured":"Frischmeyer-Guerrerio, P. A. et al. TGF\u03b2 receptor mutations impose a strong predisposition for human allergic disease. Sci. Transl. Med. 5, 195ra194 (2013).","journal-title":"Sci. Transl. Med."},{"key":"1086_CR3","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-26939-9","volume":"12","author":"T Shoda","year":"2021","unstructured":"Shoda, T. et al. Desmoplakin and periplakin genetically and functionally contribute to eosinophilic esophagitis. Nat. Commun. 12, 6795 (2021).","journal-title":"Nat. Commun."},{"key":"1086_CR4","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.jaci.2019.11.005","volume":"145","author":"D Simon","year":"2020","unstructured":"Simon, D. & Simon, H. U. Relationship of skin barrier breakdown and eosinophilic esophagitis. J. Allergy Clin. Immunol. 145, 90\u201392.e1 (2020).","journal-title":"J. Allergy Clin. Immunol."},{"key":"1086_CR5","doi-asserted-by":"publisher","first-page":"2003","DOI":"10.1016\/j.jaci.2016.10.045","volume":"139","author":"C Paluel-Marmont","year":"2017","unstructured":"Paluel-Marmont, C. et al. Eosinophilic esophagitis and colonic mucosal eosinophilia in Netherton syndrome. J. Allergy Clin. Immunol. 139, 2003\u20132005.e1 (2017).","journal-title":"J. Allergy Clin. Immunol."},{"key":"1086_CR6","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.jaci.2018.05.008","volume":"142","author":"M Rochman","year":"2018","unstructured":"Rochman, M., Azouz, N. P. & Rothenberg, M. E. Epithelial origin of eosinophilic esophagitis. J. Allergy Clin. Immunol. 142, 10\u201323 (2018).","journal-title":"J. Allergy Clin. Immunol."},{"key":"1086_CR7","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1016\/j.jaci.2006.05.004","volume":"118","author":"S Weidinger","year":"2006","unstructured":"Weidinger, S. et al. Loss-of-function variations within the filaggrin gene predispose for atopic dermatitis with allergic sensitizations. J. Allergy Clin. Immunol. 118, 214\u2013219 (2006).","journal-title":"J. Allergy Clin. Immunol."},{"key":"1086_CR8","doi-asserted-by":"publisher","first-page":"988","DOI":"10.1016\/j.jaci.2021.08.018","volume":"149","author":"X Chang","year":"2022","unstructured":"Chang, X. et al. A genome-wide association meta-analysis identifies new eosinophilic esophagitis loci. J. Allergy Clin. Immunol. 149, 988\u2013998 (2022).","journal-title":"J. Allergy Clin. Immunol."},{"key":"1086_CR9","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1038\/ng.3033","volume":"46","author":"LC Kottyan","year":"2014","unstructured":"Kottyan, L. C. et al. Genome-wide association analysis of eosinophilic esophagitis provides insight into the tissue specificity of this allergic disease. Nat. Genet. 46, 895\u2013900 (2014).","journal-title":"Nat. Genet."},{"key":"1086_CR10","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/j.jaci.2020.10.018","volume":"147","author":"LC Kottyan","year":"2021","unstructured":"Kottyan, L. C. et al. Replication and meta-analyses nominate numerous eosinophilic esophagitis risk genes. J. Allergy Clin. Immunol. 147, 255\u2013266 (2021).","journal-title":"J. Allergy Clin. Immunol."},{"key":"1086_CR11","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6593","volume":"5","author":"PM Sleiman","year":"2014","unstructured":"Sleiman, P. M. et al. GWAS identifies four novel eosinophilic esophagitis loci. Nat. Commun. 5, 5593 (2014).","journal-title":"Nat. Commun."},{"key":"1086_CR12","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-47647-0","volume":"15","author":"J Ding","year":"2024","unstructured":"Ding, J. et al. An esophagus cell atlas reveals dynamic rewiring during active eosinophilic esophagitis and remission. Nat. Commun. 15, 3344 (2024).","journal-title":"Nat. Commun."},{"key":"1086_CR13","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-17541-5","volume":"7","author":"J Travers","year":"2017","unstructured":"Travers, J. et al. IL-33 is induced in undifferentiated, non-dividing esophageal epithelial cells in eosinophilic esophagitis. Sci. Rep. 7, 17563 (2017).","journal-title":"Sci. Rep."},{"key":"1086_CR14","doi-asserted-by":"publisher","first-page":"4758","DOI":"10.1111\/febs.16103","volume":"289","author":"T Kaymak","year":"2022","unstructured":"Kaymak, T., Hruz, P. & Niess, J. H. Immune system and microbiome in the esophagus: implications for understanding inflammatory diseases. FEBS J. 289, 4758\u20134772 (2022).","journal-title":"FEBS J."},{"key":"1086_CR15","doi-asserted-by":"publisher","first-page":"595762","DOI":"10.3389\/fimmu.2021.595762","volume":"12","author":"M Mennini","year":"2021","unstructured":"Mennini, M. et al. Eosinophilic esophagitis and microbiota: state of the art. Front. Immunol. 12, 595762 (2021).","journal-title":"Front. Immunol."},{"key":"1086_CR16","doi-asserted-by":"publisher","first-page":"G216","DOI":"10.1152\/ajpgi.00088.2015","volume":"309","author":"SL Rosekrans","year":"2015","unstructured":"Rosekrans, S. L., Baan, B., Muncan, V. & van den Brink, G. R. Esophageal development and epithelial homeostasis. Am. J. Physiol. Gastrointest. Liver Physiol. 309, G216\u2013G228 (2015).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"1086_CR17","doi-asserted-by":"publisher","first-page":"dev193839","DOI":"10.1242\/dev.193839","volume":"148","author":"Y Zhang","year":"2021","unstructured":"Zhang, Y., Bailey, D., Yang, P., Kim, E. & Que, J. The development and stem cells of the esophagus. Development 148, dev193839 (2021).","journal-title":"Development"},{"key":"1086_CR18","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1053\/j.gastro.2021.10.002","volume":"162","author":"M Brusilovsky","year":"2022","unstructured":"Brusilovsky, M. et al. Host\u2013microbiota interactions in the esophagus during homeostasis and allergic inflammation. Gastroenterology 162, 521\u2013534.e8 (2022).","journal-title":"Gastroenterology"},{"key":"1086_CR19","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1007\/s11938-018-0171-5","volume":"16","author":"M May","year":"2018","unstructured":"May, M. & Abrams, J. A. Emerging insights into the esophageal microbiome. Curr. Treat. Options Gastroenterol. 16, 72\u201385 (2018).","journal-title":"Curr. Treat. Options Gastroenterol."},{"key":"1086_CR20","doi-asserted-by":"publisher","first-page":"2054","DOI":"10.3748\/wjg.v27.i18.2054","volume":"27","author":"SM D\u2019Souza","year":"2021","unstructured":"D\u2019Souza, S. M. et al. Role of microbial dysbiosis in the pathogenesis of esophageal mucosal disease: a paradigm shift from acid to bacteria? World J. Gastroenterol. 27, 2054\u20132072 (2021).","journal-title":"World J. Gastroenterol."},{"key":"1086_CR21","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1038\/s41424-018-0067-7","volume":"9","author":"YR Nobel","year":"2018","unstructured":"Nobel, Y. R. et al. Increasing dietary fiber intake is associated with a distinct esophageal microbiome. Clin. Transl. Gastroenterol. 9, 199 (2018).","journal-title":"Clin. Transl. Gastroenterol."},{"key":"1086_CR22","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.critrevonc.2017.12.006","volume":"122","author":"SS Dhanisha","year":"2018","unstructured":"Dhanisha, S. S., Guruvayoorappan, C., Drishya, S. & Abeesh, P. Mucins: structural diversity, biosynthesis, its role in pathogenesis and as possible therapeutic targets. Crit. Rev. Oncol. Hematol. 122, 98\u2013122 (2018).","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"1086_CR23","doi-asserted-by":"publisher","first-page":"2575","DOI":"10.1111\/j.1572-0241.2001.04159.x","volume":"96","author":"J Dixon","year":"2001","unstructured":"Dixon, J. et al. Esophageal mucin: an adherent mucus gel barrier is absent in the normal esophagus but present in columnar-lined Barrett\u2019s esophagus. Am. J. Gastroenterol. 96, 2575\u20132583 (2001).","journal-title":"Am. J. Gastroenterol."},{"key":"1086_CR24","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1038\/nrgastro.2011.211","volume":"9","author":"Y Niv","year":"2011","unstructured":"Niv, Y. & Fass, R. The role of mucin in GERD and its complications. Nat. Rev. Gastroenterol. Hepatol. 9, 55\u201359 (2011).","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"1086_CR25","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1038\/s41420-022-01006-4","volume":"8","author":"Y Tian","year":"2022","unstructured":"Tian, Y. et al. Mucin 21 confers resistance to apoptosis in an O-glycosylation-dependent manner. Cell Death Discov. 8, 194 (2022).","journal-title":"Cell Death Discov."},{"key":"1086_CR26","doi-asserted-by":"publisher","first-page":"1218","DOI":"10.1093\/glycob\/cws082","volume":"22","author":"Y Tian","year":"2012","unstructured":"Tian, Y. et al. Mucin 21 in esophageal squamous epithelia and carcinomas: analysis with glycoform-specific monoclonal antibodies. Glycobiology 22, 1218\u20131226 (2012).","journal-title":"Glycobiology"},{"key":"1086_CR27","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1016\/0016-5085(94)90756-0","volume":"106","author":"Z Namiot","year":"1994","unstructured":"Namiot, Z., Sarosiek, J., Rourk, R. M., Hetzel, D. P. & McCallum, R. W. Human esophageal secretion: mucosal response to luminal acid and pepsin. Gastroenterology 106, 973\u2013981 (1994).","journal-title":"Gastroenterology"},{"key":"1086_CR28","doi-asserted-by":"publisher","first-page":"6295","DOI":"10.2147\/CMAR.S182436","volume":"10","author":"Y Wang","year":"2018","unstructured":"Wang, Y., Zhu, L., Xia, W. & Wang, F. Anatomy of lymphatic drainage of the esophagus and lymph node metastasis of thoracic esophageal cancer. Cancer Manag. Res. 10, 6295\u20136303 (2018).","journal-title":"Cancer Manag. Res."},{"key":"1086_CR29","doi-asserted-by":"publisher","first-page":"1406","DOI":"10.1016\/j.jtcvs.2008.08.069","volume":"137","author":"S Yajin","year":"2009","unstructured":"Yajin, S., Murakami, G., Takeuchi, H., Hasegawa, T. & Kitano, H. The normal configuration and interindividual differences in intramural lymphatic vessels of the esophagus. J. Thorac. Cardiovasc. Surg. 137, 1406\u20131414 (2009).","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"1086_CR30","doi-asserted-by":"publisher","first-page":"738","DOI":"10.1016\/j.jaci.2016.11.042","volume":"140","author":"M Rochman","year":"2017","unstructured":"Rochman, M. et al. Profound loss of esophageal tissue differentiation in patients with eosinophilic esophagitis. J. Allergy Clin. Immunol. 140, 738\u2013749.e3 (2017).","journal-title":"J. Allergy Clin. Immunol."},{"key":"1086_CR31","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.159093","volume":"7","author":"M Rochman","year":"2022","unstructured":"Rochman, M. et al. Single-cell RNA-Seq of human esophageal epithelium in homeostasis and allergic inflammation. JCI Insight 7, e159093 (2022).","journal-title":"JCI Insight"},{"key":"1086_CR32","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1016\/j.cgh.2017.06.035","volume":"16","author":"CH Blevins","year":"2018","unstructured":"Blevins, C. H., Iyer, P. G., Vela, M. F. & Katzka, D. A. The esophageal epithelial barrier in health and disease. Clin. Gastroenterol. Hepatol. 16, 608\u2013617 (2018).","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"1086_CR33","doi-asserted-by":"publisher","first-page":"566","DOI":"10.3390\/ijms21020566","volume":"21","author":"MC Mechin","year":"2020","unstructured":"Mechin, M. C., Takahara, H. & Simon, M. Deimination and peptidylarginine deiminases in skin physiology and diseases. Int. J. Mol. Sci. 21, 566 (2020).","journal-title":"Int. J. Mol. Sci."},{"key":"1086_CR34","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1111\/j.0022-202X.2005.23627.x","volume":"124","author":"RL Eckert","year":"2005","unstructured":"Eckert, R. L., Sturniolo, M. T., Broome, A. M., Ruse, M. & Rorke, E. A. Transglutaminase function in epidermis. J. Invest. Dermatol. 124, 481\u2013492 (2005).","journal-title":"J. Invest. Dermatol."},{"key":"1086_CR35","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1159\/000336619","volume":"4","author":"F Semple","year":"2012","unstructured":"Semple, F. & Dorin, J. R. \u03b2-Defensins: multifunctional modulators of infection, inflammation and more? J. Innate Immun. 4, 337\u2013348 (2012).","journal-title":"J. Innate Immun."},{"key":"1086_CR36","doi-asserted-by":"publisher","first-page":"764","DOI":"10.3389\/fimmu.2020.00764","volume":"11","author":"D Xu","year":"2020","unstructured":"Xu, D. & Lu, W. Defensins: a double-edged sword in host immunity. Front. Immunol. 11, 764 (2020).","journal-title":"Front. Immunol."},{"key":"1086_CR37","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1016\/0014-5793(96)01123-4","volume":"396","author":"C Zhao","year":"1996","unstructured":"Zhao, C., Wang, I. & Lehrer, R. I. Widespread expression of beta-defensin hBD-1 in human secretory glands and epithelial cells. FEBS Lett. 396, 319\u2013322 (1996).","journal-title":"FEBS Lett."},{"key":"1086_CR38","doi-asserted-by":"publisher","first-page":"714","DOI":"10.1165\/ajrcmb.22.6.4023","volume":"22","author":"J Harder","year":"2000","unstructured":"Harder, J. et al. Mucoid Pseudomonas aeruginosa, TNF-\u03b1, and IL-1\u03b2, but not IL-6, induce human \u03b2-defensin-2 in respiratory epithelia. Am. J. Respir. Cell Mol. Biol. 22, 714\u2013721 (2000).","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"1086_CR39","doi-asserted-by":"publisher","first-page":"2907","DOI":"10.1128\/IAI.68.5.2907-2915.2000","volume":"68","author":"S Krisanaprakornkit","year":"2000","unstructured":"Krisanaprakornkit, S. et al. Inducible expression of human \u03b2-defensin 2 by Fusobacterium nucleatum in oral epithelial cells: multiple signaling pathways and role of commensal bacteria in innate immunity and the epithelial barrier. Infect. Immun. 68, 2907\u20132915 (2000).","journal-title":"Infect. Immun."},{"key":"1086_CR40","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1038\/pr.2013.23","volume":"73","author":"S Schroeder","year":"2013","unstructured":"Schroeder, S. et al. Esophageal human \u03b2-defensin expression in eosinophilic esophagitis. Pediatr. Res. 73, 647\u2013654 (2013).","journal-title":"Pediatr. Res."},{"key":"1086_CR41","doi-asserted-by":"publisher","first-page":"46779","DOI":"10.1074\/jbc.M207587200","volume":"277","author":"J Harder","year":"2002","unstructured":"Harder, J. & Schroder, J. M. RNase 7, a novel innate immune defense antimicrobial protein of healthy human skin. J. Biol. Chem. 277, 46779\u201346784 (2002).","journal-title":"J. Biol. Chem."},{"key":"1086_CR42","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1186\/rr18","volume":"1","author":"JM Sallenave","year":"2000","unstructured":"Sallenave, J. M. The role of secretory leukocyte proteinase inhibitor and elafin (elastase-specific inhibitor\/skin-derived antileukoprotease) as alarm antiproteinases in inflammatory lung disease. Respir. Res. 1, 87\u201392 (2000).","journal-title":"Respir. Res."},{"key":"1086_CR43","doi-asserted-by":"publisher","first-page":"23658","DOI":"10.18632\/oncotarget.8151","volume":"7","author":"H Huhta","year":"2016","unstructured":"Huhta, H. et al. Toll-like receptors 1, 2, 4 and 6 in esophageal epithelium, Barrett\u2019s esophagus, dysplasia and adenocarcinoma. Oncotarget 7, 23658\u201323667 (2016).","journal-title":"Oncotarget"},{"key":"1086_CR44","doi-asserted-by":"publisher","first-page":"1437","DOI":"10.2147\/JIR.S348786","volume":"15","author":"R Su","year":"2022","unstructured":"Su, R. et al. TLR3 expression is a potential prognosis biomarker and shapes the immune-active tumor microenvironment in esophageal squamous cell carcinoma. J. Inflamm. Res. 15, 1437\u20131456 (2022).","journal-title":"J. Inflamm. Res."},{"key":"1086_CR45","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1038\/s41424-018-0017-4","volume":"9","author":"A Arias","year":"2018","unstructured":"Arias, A. et al. Toll-like receptors-mediated pathways activate inflammatory responses in the esophageal mucosa of adult eosinophilic esophagitis. Clin. Transl. Gastroenterol. 9, 147 (2018).","journal-title":"Clin. Transl. Gastroenterol."},{"key":"1086_CR46","doi-asserted-by":"publisher","first-page":"2296","DOI":"10.1016\/j.immuni.2024.09.002","volume":"57","author":"Y Liu","year":"2024","unstructured":"Liu, Y. et al. The transcription regulators ZNF750 and LSD1\/KDM1A dampen inflammation on the skin\u2019s surface by silencing pattern recognition receptors. Immunity 57, 2296\u20132309.e5 (2024).","journal-title":"Immunity"},{"key":"1086_CR47","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20190314","volume":"217","author":"AH Chan","year":"2020","unstructured":"Chan, A. H. & Schroder, K. Inflammasome signaling and regulation of interleukin-1 family cytokines. J. Exp. Med. 217, e20190314 (2020).","journal-title":"J. Exp. Med."},{"key":"1086_CR48","doi-asserted-by":"publisher","first-page":"eaaz7773","DOI":"10.1126\/scitranslmed.aaz7773","volume":"12","author":"NP Azouz","year":"2020","unstructured":"Azouz, N. P. et al. Functional role of kallikrein 5 and proteinase-activated receptor 2 in eosinophilic esophagitis. Sci. Transl. Med. 12, eaaz7773 (2020).","journal-title":"Sci. Transl. Med."},{"key":"1086_CR49","doi-asserted-by":"publisher","first-page":"eaap9736","DOI":"10.1126\/scitranslmed.aap9736","volume":"10","author":"NP Azouz","year":"2018","unstructured":"Azouz, N. P. et al. The antiprotease SPINK7 serves as an inhibitory checkpoint for esophageal epithelial inflammatory responses. Sci. Transl. Med. 10, eaap9736 (2018).","journal-title":"Sci. Transl. Med."},{"key":"1086_CR50","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-39907-8","volume":"13","author":"S Muthupalani","year":"2023","unstructured":"Muthupalani, S. et al. IL-1\u03b2 transgenic mouse model of inflammation driven esophageal and oral squamous cell carcinoma. Sci. Rep. 13, 12732 (2023).","journal-title":"Sci. Rep."},{"key":"1086_CR51","doi-asserted-by":"publisher","first-page":"1355","DOI":"10.1016\/j.jaci.2024.01.017","volume":"153","author":"MY Masuda","year":"2024","unstructured":"Masuda, M. Y. et al. Epithelial overexpression of IL-33 induces eosinophilic esophagitis dependent on IL-13. J. Allergy Clin. Immunol. 153, 1355\u20131368 (2024).","journal-title":"J. Allergy Clin. Immunol."},{"key":"1086_CR52","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1038\/icb.2015.30","volume":"93","author":"P Dutt","year":"2015","unstructured":"Dutt, P. et al. Allergen-induced interleukin-18 promotes experimental eosinophilic oesophagitis in mice. Immunol. Cell Biol. 93, 849\u2013857 (2015).","journal-title":"Immunol. Cell Biol."},{"key":"1086_CR53","doi-asserted-by":"publisher","first-page":"2014","DOI":"10.1172\/JCI125917","volume":"129","author":"T Wen","year":"2019","unstructured":"Wen, T. et al. Single-cell RNA sequencing identifies inflammatory tissue T cells in eosinophilic esophagitis. J. Clin. Invest. 129, 2014\u20132028 (2019).","journal-title":"J. Clin. Invest."},{"key":"1086_CR54","doi-asserted-by":"publisher","first-page":"1778","DOI":"10.1053\/j.gastro.2020.07.035","volume":"159","author":"MC Manresa","year":"2020","unstructured":"Manresa, M. C. et al. Increased production of LIGHT by T cells in eosinophilic esophagitis promotes differentiation of esophageal fibroblasts toward an inflammatory phenotype. Gastroenterology 159, 1778\u20131792.e13 (2020).","journal-title":"Gastroenterology"},{"key":"1086_CR55","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2200326","author":"MC Manresa","year":"2022","unstructured":"Manresa, M. C. et al. A deficiency in the cytokine TNFSF14\/LIGHT limits inflammation and remodeling in murine eosinophilic esophagitis. J. Immunol. https:\/\/doi.org\/10.4049\/jimmunol.2200326 (2022).","journal-title":"J. Immunol."},{"key":"1086_CR56","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.jaci.2018.04.015","volume":"142","author":"ET Jensen","year":"2018","unstructured":"Jensen, E. T. & Dellon, E. S. Environmental factors and eosinophilic esophagitis. J. Allergy Clin. Immunol. 142, 32\u201340 (2018).","journal-title":"J. Allergy Clin. Immunol."},{"key":"1086_CR57","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.1016\/j.jaci.2014.07.021","volume":"134","author":"ES Alexander","year":"2014","unstructured":"Alexander, E. S. et al. Twin and family studies reveal strong environmental and weaker genetic cues explaining heritability of eosinophilic esophagitis. J. Allergy Clin. Immunol. 134, 1084\u20131092.e1 (2014).","journal-title":"J. Allergy Clin. Immunol."},{"key":"1086_CR58","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1038\/s41577-019-0125-8","volume":"19","author":"V Rothhammer","year":"2019","unstructured":"Rothhammer, V. & Quintana, F. J. The aryl hydrocarbon receptor: an environmental sensor integrating immune responses in health and disease. Nat. Rev. Immunol. 19, 184\u2013197 (2019).","journal-title":"Nat. Rev. Immunol."},{"key":"1086_CR59","doi-asserted-by":"publisher","first-page":"3559","DOI":"10.3390\/cells10123559","volume":"10","author":"M Napolitano","year":"2021","unstructured":"Napolitano, M. et al. Role of aryl hydrocarbon receptor activation in inflammatory chronic skin diseases. Cells 10, 3559 (2021).","journal-title":"Cells"},{"key":"1086_CR60","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1007\/s12016-020-08789-3","volume":"59","author":"L Pernomian","year":"2020","unstructured":"Pernomian, L., Duarte-Silva, M. & de Barros Cardoso, C. R. The aryl hydrocarbon receptor (AHR) as a potential target for the control of intestinal inflammation: insights from an immune and bacteria sensor receptor. Clin. Rev. Allergy Immunol. 59, 382\u2013390 (2020).","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"1086_CR61","doi-asserted-by":"publisher","unstructured":"Azouz, N. P. et al. Aryl hydrocarbon receptor suppresses eosinophilic esophagitis responses through OVOL1 and SPINK7. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/2023.05.17.541192 (2023).","DOI":"10.1101\/2023.05.17.541192"},{"key":"1086_CR62","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1016\/j.molcel.2011.06.006","volume":"43","author":"T Tenev","year":"2011","unstructured":"Tenev, T. et al. The ripoptosome, a signaling platform that assembles in response to genotoxic stress and loss of IAPs. Mol. Cell 43, 432\u2013448 (2011).","journal-title":"Mol. Cell"},{"key":"1086_CR63","doi-asserted-by":"publisher","first-page":"1316","DOI":"10.1038\/s41590-021-01011-2","volume":"22","author":"M Brusilovsky","year":"2021","unstructured":"Brusilovsky, M. et al. Environmental allergens trigger type 2 inflammation through ripoptosome activation. Nat. Immunol. 22, 1316\u20131326 (2021).","journal-title":"Nat. Immunol."},{"key":"1086_CR64","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1016\/j.jaci.2015.05.048","volume":"136","author":"TA Doherty","year":"2015","unstructured":"Doherty, T. A. et al. Group 2 innate lymphocytes (ILC2) are enriched in active eosinophilic esophagitis. J. Allergy Clin. Immunol. 136, 792\u2013794.e3 (2015).","journal-title":"J. Allergy Clin. Immunol."},{"key":"1086_CR65","doi-asserted-by":"publisher","first-page":"2062","DOI":"10.1016\/j.jaci.2022.02.025","volume":"149","author":"N Ben-Baruch Morgenstern","year":"2022","unstructured":"Ben-Baruch Morgenstern, N. et al. Single-cell RNA sequencing of mast cells in eosinophilic esophagitis reveals heterogeneity, local proliferation, and activation that persists in remission. J. Allergy Clin. Immunol. 149, 2062\u20132077 (2022).","journal-title":"J. Allergy Clin. Immunol."},{"key":"1086_CR66","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1016\/j.it.2022.09.006","volume":"43","author":"Z Yin","year":"2022","unstructured":"Yin, Z., Zhou, Y., Turnquist, H. R. & Liu, Q. Neuro-epithelial-ILC2 crosstalk in barrier tissues. Trends Immunol. 43, 901\u2013916 (2022).","journal-title":"Trends Immunol."},{"key":"1086_CR67","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1038\/s41423-024-01242-x","volume":"22","author":"M Lim","year":"2025","unstructured":"Lim, M. et al. Esophageal ILC2s mediate abnormal epithelial remodeling in eosinophilic esophagitis via Areg-EGFR signaling. Cell Mol. Immunol. 22, 97\u2013110 (2025).","journal-title":"Cell Mol. Immunol."},{"key":"1086_CR68","doi-asserted-by":"publisher","first-page":"10762","DOI":"10.1073\/pnas.1509070112","volume":"112","author":"LA Monticelli","year":"2015","unstructured":"Monticelli, L. A. et al. IL-33 promotes an innate immune pathway of intestinal tissue protection dependent on amphiregulin-EGFR interactions. Proc. Natl Acad. Sci. USA 112, 10762\u201310767 (2015).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1086_CR69","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2024.09.025","author":"D Grommisch","year":"2024","unstructured":"Grommisch, D. et al. Regionalized cell and gene signatures govern esophageal epithelial homeostasis. Dev. Cell https:\/\/doi.org\/10.1016\/j.devcel.2024.09.025 (2024).","journal-title":"Dev. Cell"},{"key":"1086_CR70","doi-asserted-by":"publisher","first-page":"2921","DOI":"10.1016\/j.celrep.2017.08.078","volume":"20","author":"BV Kumar","year":"2017","unstructured":"Kumar, B. V. et al. Human tissue-resident memory T cells are defined by core transcriptional and functional signatures in lymphoid and mucosal sites. Cell Rep. 20, 2921\u20132934 (2017).","journal-title":"Cell Rep."},{"key":"1086_CR71","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1038\/s41586-024-08466-x","volume":"639","author":"M Reina-Campos","year":"2025","unstructured":"Reina-Campos, M. et al. Tissue-resident memory CD8 T cell diversity is spatiotemporally imprinted. Nature 639, 483\u2013492 (2025).","journal-title":"Nature"},{"key":"1086_CR72","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1159\/000357004","volume":"32","author":"SS Aceves","year":"2014","unstructured":"Aceves, S. S. Remodeling and fibrosis in chronic eosinophil inflammation. Dig. Dis. 32, 15\u201321 (2014).","journal-title":"Dig. Dis."},{"key":"1086_CR73","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1053\/j.gastro.2017.06.065","volume":"154","author":"KM O\u2019Shea","year":"2018","unstructured":"O\u2019Shea, K. M. et al. Pathophysiology of eosinophilic esophagitis. Gastroenterology 154, 333\u2013345 (2018).","journal-title":"Gastroenterology"},{"key":"1086_CR74","doi-asserted-by":"publisher","first-page":"AB204","DOI":"10.1016\/j.jaci.2021.12.671","volume":"149","author":"A Wu","year":"2022","unstructured":"Wu, A. et al. Esophageal fibroblasts are the players in the interferon response in eosinophilic esophagitis. J. Allergy Clin. Immunol. 149, AB204 (2022).","journal-title":"J. Allergy Clin. Immunol."},{"key":"1086_CR75","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1038\/s41385-021-00472-w","volume":"15","author":"MC Manresa","year":"2022","unstructured":"Manresa, M. C. et al. LIGHT controls distinct homeostatic and inflammatory gene expression profiles in esophageal fibroblasts via differential HVEM and LT\u03b2R-mediated mechanisms. Mucosal Immunol. 15, 327\u2013337 (2022).","journal-title":"Mucosal Immunol."},{"key":"1086_CR76","doi-asserted-by":"publisher","first-page":"1270","DOI":"10.1016\/j.jaci.2015.09.020","volume":"137","author":"E Tkachenko","year":"2016","unstructured":"Tkachenko, E. et al. Rigid substrate induces esophageal smooth muscle hypertrophy and eosinophilic esophagitis fibrotic gene expression. J. Allergy Clin. Immunol. 137, 1270\u20131272.e1 (2016).","journal-title":"J. Allergy Clin. Immunol."},{"key":"1086_CR77","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1097\/MPG.0000000000001100","volume":"63","author":"AB Muir","year":"2016","unstructured":"Muir, A. B. et al. Eosinophilic esophagitis-associated chemical and mechanical microenvironment shapes esophageal fibroblast behavior. J. Pediatr. Gastroenterol. Nutr. 63, 200\u2013209 (2016).","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"1086_CR78","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.jaci.2018.10.067","volume":"144","author":"Y Kasagi","year":"2019","unstructured":"Kasagi, Y. et al. Fibrostenotic eosinophilic esophagitis might reflect epithelial lysyl oxidase induction by fibroblast-derived TNF-\u03b1. J. Allergy Clin. Immunol. 144, 171\u2013182 (2019).","journal-title":"J. Allergy Clin. Immunol."},{"key":"1086_CR79","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1016\/j.jaci.2016.02.028","volume":"138","author":"R Rawson","year":"2016","unstructured":"Rawson, R. et al. TGF-\u03b21-induced PAI-1 contributes to a profibrotic network in patients with eosinophilic esophagitis. J. Allergy Clin. Immunol. 138, 791\u2013800.e4 (2016).","journal-title":"J. Allergy Clin. Immunol."},{"key":"1086_CR80","doi-asserted-by":"publisher","first-page":"1719","DOI":"10.1016\/j.cgh.2021.11.002","volume":"20","author":"DA Carlson","year":"2022","unstructured":"Carlson, D. A. et al. Esophageal dysmotility is associated with disease severity in eosinophilic esophagitis. Clin. Gastroenterol. Hepatol. 20, 1719\u20131728.e3 (2022).","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"1086_CR81","doi-asserted-by":"publisher","first-page":"486","DOI":"10.5056\/jnm21246","volume":"29","author":"L Yao","year":"2023","unstructured":"Yao, L. et al. Imbalance of innate and adaptive immunity in esophageal achalasia. J. Neurogastroenterol. Motil. 29, 486\u2013500 (2023).","journal-title":"J. Neurogastroenterol. Motil."},{"key":"1086_CR82","doi-asserted-by":"publisher","first-page":"1257266","DOI":"10.3389\/fonc.2023.1257266","volume":"13","author":"M Xue","year":"2023","unstructured":"Xue, M., Tong, Y., Xiong, Y. & Yu, C. Role of cancer-associated fibroblasts in the progression, therapeutic resistance and targeted therapy of oesophageal squamous cell carcinoma. Front. Oncol. 13, 1257266 (2023).","journal-title":"Front. Oncol."},{"key":"1086_CR83","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1053\/j.gastro.2021.10.016","volume":"162","author":"T Shoda","year":"2022","unstructured":"Shoda, T. et al. Loss of endothelial TSPAN12 promotes fibrostenotic eosinophilic esophagitis via endothelial cell-fibroblast crosstalk. Gastroenterology 162, 439\u2013453 (2022).","journal-title":"Gastroenterology"},{"key":"1086_CR84","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/j.lfs.2013.12.024","volume":"118","author":"F Rodriguez-Pascual","year":"2014","unstructured":"Rodriguez-Pascual, F., Busnadiego, O. & Gonzalez-Santamaria, J. The profibrotic role of endothelin-1: is the door still open for the treatment of fibrotic diseases? Life Sci. 118, 156\u2013164 (2014).","journal-title":"Life Sci."},{"key":"1086_CR85","doi-asserted-by":"publisher","first-page":"102458","DOI":"10.1016\/j.coi.2024.102458","volume":"90","author":"IM Chiu","year":"2024","unstructured":"Chiu, I. M. & Sokol, C. L. Neuroimmune recognition of allergens. Curr. Opin. Immunol. 90, 102458 (2024).","journal-title":"Curr. Opin. Immunol."},{"key":"1086_CR86","doi-asserted-by":"publisher","first-page":"3326","DOI":"10.1111\/all.16366","volume":"79","author":"V Houghton","year":"2024","unstructured":"Houghton, V. et al. From bite to brain: neuro-immune interactions in food allergy. Allergy 79, 3326\u20133340 (2024).","journal-title":"Allergy"},{"key":"1086_CR87","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1016\/j.jaci.2023.08.017","volume":"153","author":"B Kim","year":"2024","unstructured":"Kim, B. et al. Neuroimmune interplay during type 2 inflammation: symptoms, mechanisms, and therapeutic targets in atopic diseases. J. Allergy Clin. Immunol. 153, 879\u2013893 (2024).","journal-title":"J. Allergy Clin. Immunol."},{"key":"1086_CR88","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/s41232-024-00352-3","volume":"44","author":"M Izumi","year":"2024","unstructured":"Izumi, M., Nakanishi, Y., Kang, S. & Kumanogoh, A. Peripheral and central regulation of neuro-immune crosstalk. Inflamm. Regen. 44, 41 (2024).","journal-title":"Inflamm. Regen."},{"key":"1086_CR89","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1038\/nrgastro.2012.32","volume":"9","author":"JB Furness","year":"2012","unstructured":"Furness, J. B. The enteric nervous system and neurogastroenterology. Nat. Rev. Gastroenterol. Hepatol. 9, 286\u2013294 (2012).","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"1086_CR90","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1007\/s00535-023-02065-9","volume":"59","author":"T Leech","year":"2024","unstructured":"Leech, T. & Peiris, M. Mucosal neuroimmune mechanisms in gastro-oesophageal reflux disease (GORD) pathogenesis. J. Gastroenterol. 59, 165\u2013178 (2024).","journal-title":"J. Gastroenterol."},{"key":"1086_CR91","doi-asserted-by":"publisher","first-page":"87S","DOI":"10.1016\/S0002-9343(99)00344-7","volume":"108","author":"JN Sengupta","year":"2000","unstructured":"Sengupta, J. N. An overview of esophageal sensory receptors. Am. J. Med. 108, 87S\u201389S (2000).","journal-title":"Am. J. Med."},{"key":"1086_CR92","doi-asserted-by":"publisher","first-page":"G471","DOI":"10.1152\/ajpgi.00156.2014","volume":"307","author":"X Yu","year":"2014","unstructured":"Yu, X., Hu, Y. & Yu, S. Effects of acid on vagal nociceptive afferent subtypes in guinea pig esophagus. Am. J. Physiol. Gastrointest. Liver Physiol. 307, G471\u2013G478 (2014).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"1086_CR93","doi-asserted-by":"publisher","first-page":"1606","DOI":"10.1016\/j.cell.2020.08.003","volume":"182","author":"E Drokhlyansky","year":"2020","unstructured":"Drokhlyansky, E. et al. The human and mouse enteric nervous system at single-cell resolution. Cell 182, 1606\u20131622.e3 (2020).","journal-title":"Cell"},{"key":"1086_CR94","doi-asserted-by":"publisher","first-page":"2184","DOI":"10.1016\/j.neuron.2023.04.025","volume":"111","author":"ED Lowenstein","year":"2023","unstructured":"Lowenstein, E. D. et al. Prox2 and Runx3 vagal sensory neurons regulate esophageal motility. Neuron 111, 2184\u20132200.e7 (2023).","journal-title":"Neuron"},{"key":"1086_CR95","doi-asserted-by":"publisher","first-page":"G525","DOI":"10.1152\/ajpgi.00175.2014","volume":"308","author":"P Woodland","year":"2015","unstructured":"Woodland, P. et al. Distinct afferent innervation patterns within the human proximal and distal esophageal mucosa. Am. J. Physiol. Gastrointest. Liver Physiol. 308, G525\u2013G531 (2015).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"1086_CR96","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-41147-8","volume":"9","author":"RC Kurten","year":"2019","unstructured":"Kurten, R. C. et al. Development and application of a functional human esophageal mucosa explant platform to eosinophilic esophagitis. Sci. Rep. 9, 6206 (2019).","journal-title":"Sci. Rep."},{"key":"1086_CR97","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1016\/j.mucimm.2024.10.001","volume":"17","author":"Z Wang","year":"2024","unstructured":"Wang, Z., Song, K., Kim, B. S. & Manion, J. Sensory neuroimmune interactions at the barrier. Mucosal Immunol. 17, 1151\u20131160 (2024).","journal-title":"Mucosal Immunol."},{"key":"1086_CR98","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1016\/j.immuni.2020.10.001","volume":"53","author":"C Perner","year":"2020","unstructured":"Perner, C. et al. Substance P release by sensory neurons triggers dendritic cell migration and initiates the type-2 immune response to allergens. Immunity 53, 1063\u20131077.e7 (2020).","journal-title":"Immunity"},{"key":"1086_CR99","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/j.cell.2017.08.006","volume":"171","author":"LK Oetjen","year":"2017","unstructured":"Oetjen, L. K. et al. Sensory neurons co-opt classical immune signaling pathways to mediate chronic itch. Cell 171, 217\u2013228.e3 (2017).","journal-title":"Cell"},{"key":"1086_CR100","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1016\/j.neuron.2015.06.007","volume":"87","author":"S Talbot","year":"2015","unstructured":"Talbot, S. et al. Silencing nociceptor neurons reduces allergic airway inflammation. Neuron 87, 341\u2013354 (2015).","journal-title":"Neuron"},{"key":"1086_CR101","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1053\/eujp.2001.0226","volume":"5","author":"W Koppert","year":"2001","unstructured":"Koppert, W., Martus, P. & Reeh, P. W. Interactions of histamine and bradykinin on polymodal C-fibres in isolated rat skin. Eur. J. Pain. 5, 97\u2013106 (2001).","journal-title":"Eur. J. Pain."},{"key":"1086_CR102","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1016\/j.it.2024.08.007","volume":"45","author":"P Hanc","year":"2024","unstructured":"Hanc, P., Messou, M. A., Ajit, J. & von Andrian, U. H. Setting the tone: nociceptors as conductors of immune responses. Trends Immunol. 45, 783\u2013798 (2024).","journal-title":"Trends Immunol."},{"key":"1086_CR103","doi-asserted-by":"publisher","first-page":"1895","DOI":"10.1111\/all.15260","volume":"77","author":"S Zhang","year":"2022","unstructured":"Zhang, S. et al. Mast cell-pain connection in eosinophilic esophagitis. Allergy 77, 1895\u20131899 (2022).","journal-title":"Allergy"},{"key":"1086_CR104","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-43717-2","volume":"9","author":"R Villanueva-Romero","year":"2019","unstructured":"Villanueva-Romero, R. et al. Activation of Th lymphocytes alters pattern expression and cellular location of VIP receptors in healthy donors and early arthritis patients. Sci. Rep. 9, 7383 (2019).","journal-title":"Sci. Rep."},{"key":"1086_CR105","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1146\/annurev-immunol-101921-042929","volume":"42","author":"A Wallrapp","year":"2024","unstructured":"Wallrapp, A. & Chiu, I. M. Neuroimmune interactions in the intestine. Annu. Rev. Immunol. 42, 489\u2013519 (2024).","journal-title":"Annu. Rev. Immunol."},{"key":"1086_CR106","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1038\/s41385-020-00368-1","volume":"14","author":"A Jacobson","year":"2021","unstructured":"Jacobson, A., Yang, D., Vella, M. & Chiu, I. M. The intestinal neuro-immune axis: crosstalk between neurons, immune cells, and microbes. Mucosal Immunol. 14, 555\u2013565 (2021).","journal-title":"Mucosal Immunol."},{"key":"1086_CR107","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1038\/s41577-019-0247-z","volume":"20","author":"JR Huh","year":"2020","unstructured":"Huh, J. R. & Veiga-Fernandes, H. Neuroimmune circuits in inter-organ communication. Nat. Rev. Immunol. 20, 217\u2013228 (2020).","journal-title":"Nat. Rev. Immunol."},{"key":"1086_CR108","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1136\/gut.44.3.317","volume":"44","author":"M Newton","year":"1999","unstructured":"Newton, M. et al. Oesophageal epithelial innervation in health and reflux oesophagitis. Gut 44, 317\u2013322 (1999).","journal-title":"Gut"},{"key":"1086_CR109","doi-asserted-by":"publisher","first-page":"2237","DOI":"10.1007\/s10620-012-2337-7","volume":"58","author":"N Yoshida","year":"2013","unstructured":"Yoshida, N. et al. Role of nociceptors\/neuropeptides in the pathogenesis of visceral hypersensitivity of nonerosive reflux disease. Dig. Dis. Sci. 58, 2237\u20132243 (2013).","journal-title":"Dig. Dis. Sci."},{"key":"1086_CR110","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1111\/j.1365-2982.2010.01514.x","volume":"22","author":"MP Guarino","year":"2010","unstructured":"Guarino, M. P. et al. Increased TRPV1 gene expression in esophageal mucosa of patients with non-erosive and erosive reflux disease. Neurogastroenterol. Motil. 22, 746\u2013751, e219 (2010).","journal-title":"Neurogastroenterol. Motil."},{"key":"1086_CR111","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1007\/s10620-012-2308-z","volume":"58","author":"X Xu","year":"2013","unstructured":"Xu, X. et al. High expression of calcitonin gene-related peptide and substance P in esophageal mucosa of patients with non-erosive reflux disease. Dig. Dis. Sci. 58, 53\u201360 (2013).","journal-title":"Dig. Dis. Sci."},{"key":"1086_CR112","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1016\/j.immuni.2024.03.008","volume":"57","author":"L Deng","year":"2024","unstructured":"Deng, L., Gillis, J. E., Chiu, I. M. & Kaplan, D. H. Sensory neurons: an integrated component of innate immunity. Immunity 57, 815\u2013831 (2024).","journal-title":"Immunity"},{"key":"1086_CR113","first-page":"L1096","volume":"273","author":"A Garland","year":"1997","unstructured":"Garland, A. et al. Activated eosinophils elicit substance P release from cultured dorsal root ganglion neurons. Am. J. Physiol. 273, L1096\u2013L1102 (1997).","journal-title":"Am. J. Physiol."},{"key":"1086_CR114","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1016\/j.jaci.2024.02.005","volume":"153","author":"C Bao","year":"2024","unstructured":"Bao, C. & Abraham, S. N. Mast cell-sensory neuron crosstalk in allergic diseases. J. Allergy Clin. Immunol. 153, 939\u2013953 (2024).","journal-title":"J. Allergy Clin. Immunol."},{"key":"1086_CR115","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1111\/nmo.12342","volume":"26","author":"T Kondo","year":"2014","unstructured":"Kondo, T. et al. Effect of rikkunshito on the expression of substance P and CGRP in dorsal root ganglion neurons and voluntary movement in rats with experimental reflux esophagitis. Neurogastroenterol. Motil. 26, 913\u2013921 (2014).","journal-title":"Neurogastroenterol. Motil."},{"key":"1086_CR116","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1007\/s10555-022-10026-6","volume":"41","author":"T Sharma","year":"2022","unstructured":"Sharma, T. et al. Cross-talk between the microbiome and chronic inflammation in esophageal cancer: potential driver of oncogenesis. Cancer Metastasis Rev. 41, 281\u2013299 (2022).","journal-title":"Cancer Metastasis Rev."},{"key":"1086_CR117","doi-asserted-by":"publisher","first-page":"G629","DOI":"10.1152\/ajpgi.00197.2024","volume":"327","author":"M Rochman","year":"2024","unstructured":"Rochman, M., Klinger, A. M., Caldwell, J. M., Sadovsky, Y. & Rothenberg, M. E. Amniotic fluid modifies esophageal epithelium differentiation and inflammatory responses. Am. J. Physiol. Gastrointest. Liver Physiol. 327, G629\u2013G639 (2024).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"1086_CR118","doi-asserted-by":"publisher","first-page":"doaa074","DOI":"10.1093\/dote\/doaa074","volume":"34","author":"ES Dellon","year":"2021","unstructured":"Dellon, E. S. et al. Early life factors are associated with risk for eosinophilic esophagitis diagnosed in adulthood. Dis. Esophagus 34, doaa074 (2021).","journal-title":"Dis. Esophagus"},{"key":"1086_CR119","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1097\/MPG.0b013e318290d15a","volume":"57","author":"ET Jensen","year":"2013","unstructured":"Jensen, E. T., Kappelman, M. D., Kim, H. P., Ringel-Kulka, T. & Dellon, E. S. Early life exposures as risk factors for pediatric eosinophilic esophagitis. J. Pediatr. Gastroenterol. Nutr. 57, 67\u201371 (2013).","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"1086_CR120","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1136\/gutjnl-2015-310861","volume":"65","author":"MA Jackson","year":"2016","unstructured":"Jackson, M. A. et al. Proton pump inhibitors alter the composition of the gut microbiota. Gut 65, 749\u2013756 (2016).","journal-title":"Gut"},{"key":"1086_CR121","doi-asserted-by":"publisher","first-page":"1924","DOI":"10.1016\/j.jaci.2020.09.039","volume":"147","author":"M Rochman","year":"2021","unstructured":"Rochman, M. et al. Broad transcriptional response of the human esophageal epithelium to proton pump inhibitors. J. Allergy Clin. Immunol. 147, 1924\u20131935 (2021).","journal-title":"J. Allergy Clin. Immunol."},{"key":"1086_CR122","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-00132-w","volume":"11","author":"H Ogiso","year":"2021","unstructured":"Ogiso, H. et al. Risk factors for the development of esophageal candidiasis among patients in community hospital. Sci. Rep. 11, 20663 (2021).","journal-title":"Sci. Rep."},{"key":"1086_CR123","doi-asserted-by":"publisher","first-page":"102428","DOI":"10.1016\/j.eclinm.2024.102428","volume":"68","author":"H Huang","year":"2024","unstructured":"Huang, H., Jiang, J., Wang, X., Jiang, K. & Cao, H. Exposure to prescribed medication in early life and impacts on gut microbiota and disease development. eClinicalMedicine 68, 102428 (2024).","journal-title":"eClinicalMedicine"},{"key":"1086_CR124","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1126\/science.aac4263","volume":"349","author":"C Ohnmacht","year":"2015","unstructured":"Ohnmacht, C. et al. Mucosal immunology. The microbiota regulates type 2 immunity through ROR\u03b3t+ T cells. Science 349, 989\u2013993 (2015).","journal-title":"Science"},{"key":"1086_CR125","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1038\/nri2515","volume":"9","author":"JL Round","year":"2009","unstructured":"Round, J. L. & Mazmanian, S. K. The gut microbiota shapes intestinal immune responses during health and disease. Nat. Rev. Immunol. 9, 313\u2013323 (2009).","journal-title":"Nat. Rev. Immunol."},{"key":"1086_CR126","doi-asserted-by":"publisher","first-page":"2635","DOI":"10.1007\/s00262-020-02650-4","volume":"69","author":"G Barber","year":"2020","unstructured":"Barber, G. et al. Characterizing caspase-1 involvement during esophageal disease progression. Cancer Immunol. Immunother. 69, 2635\u20132649 (2020).","journal-title":"Cancer Immunol. Immunother."},{"key":"1086_CR127","doi-asserted-by":"publisher","first-page":"1042","DOI":"10.1136\/gutjnl-2013-305533","volume":"63","author":"X Huo","year":"2014","unstructured":"Huo, X. et al. In oesophageal squamous cells exposed to acidic bile salt medium, omeprazole inhibits IL-8 expression through effects on nuclear factor-\u03baB and activator protein-1. Gut 63, 1042\u20131052 (2014).","journal-title":"Gut"},{"key":"1086_CR128","doi-asserted-by":"publisher","first-page":"2104","DOI":"10.1001\/jama.2016.5657","volume":"315","author":"KB Dunbar","year":"2016","unstructured":"Dunbar, K. B. et al. Association of acute gastroesophageal reflux disease with esophageal histologic changes. JAMA 315, 2104\u20132112 (2016).","journal-title":"JAMA"},{"key":"1086_CR129","doi-asserted-by":"publisher","first-page":"1776","DOI":"10.1053\/j.gastro.2009.07.055","volume":"137","author":"RF Souza","year":"2009","unstructured":"Souza, R. F. et al. Gastroesophageal reflux might cause esophagitis through a cytokine-mediated mechanism rather than caustic acid injury. Gastroenterology 137, 1776\u20131784 (2009).","journal-title":"Gastroenterology"},{"key":"1086_CR130","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01220-0","volume":"8","author":"I Marenholz","year":"2017","unstructured":"Marenholz, I. et al. Genome-wide association study identifies the SERPINB gene cluster as a susceptibility locus for food allergy. Nat. Commun. 8, 1056 (2017).","journal-title":"Nat. Commun."},{"key":"1086_CR131","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1136\/gutjnl-2021-326698","volume":"72","author":"J Schroder","year":"2023","unstructured":"Schroder, J. et al. GWAS meta-analysis of 16 790 patients with Barrett\u2019s oesophagus and oesophageal adenocarcinoma identifies 16 novel genetic risk loci and provides insights into disease aetiology beyond the single marker level. Gut 72, 612\u2013623 (2023).","journal-title":"Gut"},{"key":"1086_CR132","doi-asserted-by":"publisher","first-page":"1137","DOI":"10.1016\/j.jaci.2022.11.008","volume":"151","author":"MF Huffaker","year":"2023","unstructured":"Huffaker, M. F. et al. Epidermal differentiation complex genetic variation in atopic dermatitis and peanut allergy. J. Allergy Clin. Immunol. 151, 1137\u20131142.e4 (2023).","journal-title":"J. Allergy Clin. Immunol."},{"key":"1086_CR133","doi-asserted-by":"publisher","first-page":"3224","DOI":"10.1172\/JCI126744","volume":"129","author":"JC Masterson","year":"2019","unstructured":"Masterson, J. C. et al. Epithelial HIF-1\u03b1\/claudin-1 axis regulates barrier dysfunction in eosinophilic esophagitis. J. Clin. Invest. 129, 3224\u20133235 (2019).","journal-title":"J. Clin. Invest."},{"key":"1086_CR134","doi-asserted-by":"publisher","first-page":"1472","DOI":"10.1016\/j.jaci.2024.07.030","volume":"154","author":"S Ryan","year":"2024","unstructured":"Ryan, S. et al. Metabolic dysfunction mediated by HIF-1\u03b1 contributes to epithelial differentiation defects in eosinophilic esophagitis. J. Allergy Clin. Immunol. 154, 1472\u20131488 (2024).","journal-title":"J. Allergy Clin. Immunol."},{"key":"1086_CR135","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1097\/MPG.0000000000000343","volume":"59","author":"JY Cho","year":"2014","unstructured":"Cho, J. Y. et al. Smad3-deficient mice have reduced esophageal fibrosis and angiogenesis in a model of egg-induced eosinophilic esophagitis. J. Pediatr. Gastroenterol. Nutr. 59, 10\u201316 (2014).","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"1086_CR136","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1016\/j.jaci.2013.02.030","volume":"132","author":"JP Abonia","year":"2013","unstructured":"Abonia, J. P. et al. High prevalence of eosinophilic esophagitis in patients with inherited connective tissue disorders. J. Allergy Clin. Immunol. 132, 378\u2013386 (2013).","journal-title":"J. Allergy Clin. Immunol."},{"key":"1086_CR137","doi-asserted-by":"publisher","DOI":"10.1172\/JCI174981","volume":"135","author":"T Derakhshan","year":"2025","unstructured":"Derakhshan, T. et al. Human intraepithelial mast cell differentiation and effector function are directed by TGF-\u03b2 signaling. J. Clin. Invest. 135, e174981 (2025).","journal-title":"J. Clin. Invest."},{"key":"1086_CR138","doi-asserted-by":"publisher","first-page":"eabp9940","DOI":"10.1126\/sciimmunol.abp9940","volume":"8","author":"K Laky","year":"2023","unstructured":"Laky, K. et al. Epithelial-intrinsic defects in TGF\u03b2R signaling drive local allergic inflammation manifesting as eosinophilic esophagitis. Sci. Immunol. 8, eabp9940 (2023).","journal-title":"Sci. Immunol."},{"key":"1086_CR139","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.1016\/j.jaci.2024.12.1070","volume":"155","author":"MH Clevenger","year":"2025","unstructured":"Clevenger, M. H. et al. Esophageal epithelial Ikk\u03b2 deletion promotes eosinophilic esophagitis in experimental allergy mouse model. J. Allergy Clin. Immunol. 155, 1276\u20131289 (2025).","journal-title":"J. Allergy Clin. Immunol."},{"key":"1086_CR140","doi-asserted-by":"publisher","first-page":"1517","DOI":"10.1242\/dmm.030767","volume":"10","author":"K Eden","year":"2017","unstructured":"Eden, K., Rothschild, D. E., McDaniel, D. K., Heid, B. & Allen, I. C. Noncanonical NF-\u03baB signaling and the essential kinase NIK modulate crucial features associated with eosinophilic esophagitis pathogenesis. Dis. Model. Mech. 10, 1517\u20131527 (2017).","journal-title":"Dis. Model. Mech."},{"key":"1086_CR141","doi-asserted-by":"publisher","first-page":"4033","DOI":"10.4049\/jimmunol.0903069","volume":"184","author":"C Blanchard","year":"2010","unstructured":"Blanchard, C. et al. Coordinate interaction between IL-13 and epithelial differentiation cluster genes in eosinophilic esophagitis. J. Immunol. 184, 4033\u20134041 (2010).","journal-title":"J. Immunol."},{"key":"1086_CR142","doi-asserted-by":"publisher","first-page":"660","DOI":"10.4049\/jimmunol.1000471","volume":"185","author":"L Zuo","year":"2010","unstructured":"Zuo, L. et al. IL-13 induces esophageal remodeling and gene expression by an eosinophil-independent, IL-13R\u03b12-inhibited pathway. J. Immunol. 185, 660\u2013669 (2010).","journal-title":"J. Immunol."},{"key":"1086_CR143","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1053\/j.gastro.2018.10.051","volume":"156","author":"I Hirano","year":"2019","unstructured":"Hirano, I. et al. RPC4046, a monoclonal antibody against IL13, reduces histologic and endoscopic activity in patients with eosinophilic esophagitis. Gastroenterology 156, 592\u2013603.e10 (2019).","journal-title":"Gastroenterology"},{"key":"1086_CR144","doi-asserted-by":"publisher","first-page":"1325","DOI":"10.1016\/j.jaci.2022.09.027","volume":"150","author":"ME Rothenberg","year":"2022","unstructured":"Rothenberg, M. E. Scientific journey to the first FDA-approved drug for eosinophilic esophagitis. J. Allergy Clin. Immunol. 150, 1325\u20131332 (2022).","journal-title":"J. Allergy Clin. Immunol."},{"key":"1086_CR145","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1186\/s40880-019-0427-z","volume":"39","author":"TX Huang","year":"2019","unstructured":"Huang, T. X. & Fu, L. The immune landscape of esophageal cancer. Cancer Commun. 39, 79 (2019).","journal-title":"Cancer Commun."},{"key":"1086_CR146","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202200898R","volume":"36","author":"K Shi","year":"2022","unstructured":"Shi, K. et al. Profiling transcriptional heterogeneity of epithelium, fibroblasts, and immune cells in esophageal squamous cell carcinoma by single-cell RNA sequencing. FASEB J. 36, e22620 (2022).","journal-title":"FASEB J."},{"key":"1086_CR147","doi-asserted-by":"publisher","first-page":"2252","DOI":"10.1056\/NEJMoa2313318","volume":"390","author":"ME Rothenberg","year":"2024","unstructured":"Rothenberg, M. E. et al. Eosinophil depletion with benralizumab for eosinophilic esophagitis. N. Engl. J. Med. 390, 2252\u20132263 (2024).","journal-title":"N. Engl. J. Med."},{"key":"1086_CR148","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11968-2","volume":"10","author":"J An","year":"2019","unstructured":"An, J. et al. Gastroesophageal reflux GWAS identifies risk loci that also associate with subsequent severe esophageal diseases. Nat. Commun. 10, 4219 (2019).","journal-title":"Nat. Commun."},{"key":"1086_CR149","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1038\/ng.547","volume":"42","author":"ME Rothenberg","year":"2010","unstructured":"Rothenberg, M. E. et al. Common variants at 5q22 associate with pediatric eosinophilic esophagitis. Nat. Genet. 42, 289\u2013291 (2010).","journal-title":"Nat. Genet."},{"key":"1086_CR150","doi-asserted-by":"publisher","first-page":"1292","DOI":"10.1016\/j.jaci.2007.10.024","volume":"120","author":"C Blanchard","year":"2007","unstructured":"Blanchard, C. et al. IL-13 involvement in eosinophilic esophagitis: transcriptome analysis and reversibility with glucocorticoids. J. Allergy Clin. Immunol. 120, 1292\u20131300 (2007).","journal-title":"J. Allergy Clin. Immunol."},{"key":"1086_CR151","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1007\/s00418-016-1473-0","volume":"146","author":"CD Andl","year":"2016","unstructured":"Andl, C. D. et al. Association of TGF\u03b2 signaling with the maintenance of a quiescent stem cell niche in human oral mucosa. Histochem. Cell Biol. 146, 539\u2013555 (2016).","journal-title":"Histochem. Cell Biol."}],"container-title":["Nature Reviews Gastroenterology &amp; Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41575-025-01086-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41575-025-01086-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41575-025-01086-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,6]],"date-time":"2025-09-06T20:53:19Z","timestamp":1757191999000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41575-025-01086-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,18]]},"references-count":151,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["1086"],"URL":"https:\/\/doi.org\/10.1038\/s41575-025-01086-4","relation":{},"ISSN":["1759-5045","1759-5053"],"issn-type":[{"value":"1759-5045","type":"print"},{"value":"1759-5053","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,18]]},"assertion":[{"value":"26 May 2025","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 June 2025","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"M.E.R. is a consultant for Pulm One, Spoon Guru, ClostraBio, Serpin Pharm, Allakos, Celldex, Uniquitybio, Santa Ana Bio, EnZen Therapeutics, Bristol Myers Squibb, Astra Zeneca, Pfizer, GlaxoSmithKline, Regeneron\/Sanofi, Revolo Biotherapeutics and Guidepoint and has an equity interest in the first nine listed and royalties from reslizumab (Teva Pharmaceuticals), PEESSv2 (Mapi Research Trust) and UpToDate. M.E.R. is an inventor on patents owned by Cincinnati Children\u2019s Hospital. The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}