{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:32:06Z","timestamp":1791930726480,"version":"4.3.4"},"reference-count":75,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T00:00:00Z","timestamp":1722988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>There is growing evidence that neurogenic inflammation contributes to the pathophysiology of upper airway diseases, with nasal hyperreactivity (NHR) being a key symptom. The rare neuroendocrine cells (NECs) in the epithelium have been linked to the pathophysiology of bronchial and intestinal hyperreactivity, however their presence in the nasal mucosa and their potential role in NHR remains unclear. Therefore, we studied the presence of NECs in the nasal epithelium of controls, allergic rhinitis patients and chronic rhinosinusitis with nasal polyps patients, and their link to NHR. The expression of typical NECs markers, CHGA, ASCL1 and CGRP, were evaluated on gene and protein level in human samples using real-time quantitative PCR (RT-qPCR), western blot, immunohistochemistry fluorescence staining, RNA scope assay, flow cytometry and single cell RNA-sequencing. Furthermore, the change in peak nasal inspiratory flow after cold dry air provocation and visual analogue scale scores were used to evaluate NHR or disease severity, respectively. Limited gene expression of the NECs markers <jats:italic>CHGA<\/jats:italic> and <jats:italic>ASCL1<\/jats:italic> was measured in patients with upper airway diseases and controls. Gene expression of these markers did not correlate with NHR severity nor disease severity. <jats:italic>In vitro<\/jats:italic>, CHGA and ASCL1 expression was also evaluated in primary nasal epithelial cell cultures from patients with upper airway disease and controls using RT-qPCR and western blot. Both on gene and protein level only limited CHGA and ASCL1 expression was found. Additionally, NECs were studied in nasal biopsies of patients with upper airway diseases and controls using immunohistochemistry fluorescence staining, RNA scope and flow cytometry. Unlike in ileum samples, CHGA could not be detected in nasal biopsies of patients with upper airway diseases and control subjects. Lastly, single cell RNA-sequencing of upper airway tissue could not identify a NEC cluster. In summary, in contrast to the bronchi and gut, there is only limited evidence for the presence of NECs in the nasal mucosa, and without correlation with NHR, thereby questioning the relevance of NECs in upper airway pathology.<\/jats:p>","DOI":"10.3389\/fimmu.2024.1394539","type":"journal-article","created":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T04:23:37Z","timestamp":1723004617000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Rare presence and function of neuroendocrine cells in the nasal mucosa"],"prefix":"10.3389","volume":"15","author":[{"given":"Tine","family":"Wils","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wout","family":"Backaert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inge","family":"Jacobs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Ruysseveldt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Cremer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Dilissen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique M.","family":"Bullens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karel","family":"Talavera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brecht","family":"Steelant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Van Gerven","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katleen","family":"Martens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter W.","family":"Hellings","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,8,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1111\/all.14199","article-title":"Prevalence and impact of nasal hyperreactivity in chronic rhinosinusitis","volume":"75","author":"Doulaptsi","year":"2020","journal-title":"Allergy"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2020.01.018","article-title":"Epithelial cell function and remodeling in nasal polyposis","volume":"124","author":"Bankova","year":"2020","journal-title":"Ann Allergy Asthma Immunol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2737","article-title":"The airway epithelium in asthma","volume":"18","author":"Lambrecht","year":"2012","journal-title":"Nat Med"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1016\/j.jaci.2015.10.050","article-title":"Impaired barrier function in patients with house dust mite\u2013induced allergic rhinitis is accompanied by decreased occludin and zonula occludens-1 expression","volume":"137","author":"Steelant","year":"2016","journal-title":"J Allergy Clin Immunol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1016\/j.jaci.2011.05.038","article-title":"Defective epithelial barrier function in asthma","volume":"128","author":"Xiao","year":"2011","journal-title":"J Allergy Clin Immunol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"e0123163","DOI":"10.1371\/journal.pone.0123163","article-title":"The induction of IL-33 in the sinus epithelium and its influence on T-helper cell responses","volume":"10","author":"Soyka","year":"2012","journal-title":"PloS One"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2020.04.010","article-title":"Epithelial barriers in allergy and asthma","volume":"145","author":"Hellings","year":"2020","journal-title":"J Allergy Clin Immunol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0468-5","article-title":"A cellular census of human lungs identifies novel cell states in health and in asthma","volume":"25","author":"Vieira Braga","year":"2019","journal-title":"Nat Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0394-6","article-title":"A single-cell atlas of the airway epithelium reveals the CFTR-rich pulmonary ionocyte","volume":"560","author":"Plasschaert","year":"2018","journal-title":"Nature"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0449-8","article-title":"Allergic inflammatory memory in human respiratory epithelial progenitor cells","volume":"560","author":"Ordovas-Montanes","year":"2018","journal-title":"Nature"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2922-4","article-title":"A molecular cell atlas of the human lung from single-cell RNA sequencing","volume":"587","author":"Travaglini","year":"2020","journal-title":"Nature"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201911-2199OC","article-title":"A single-cell atlas of the human healthy airways","volume":"202","author":"Deprez","year":"2020","journal-title":"Am J Respir Crit Care Med"},{"key":"B13","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/s13601-017-0157-8","article-title":"Endotype-driven treatment in chronic upper airway diseases","volume":"7","author":"De Greve","year":"2017","journal-title":"Clin Transl Allergy"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.2500\/ajra.2014.28.4052","article-title":"Nasal allergen deposition leads to conjunctival mast cell degranulation in allergic rhinoconjunctivitis","volume":"28","author":"Callebaut","year":"2014","journal-title":"Am J Rhinol Allergy"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1111\/all.13453","article-title":"Nasal hyperreactivity in rhinitis: A diagnostic and therapeutic challenge","volume":"73","author":"Van Gerven","year":"2018","journal-title":"Allergy"},{"key":"B16","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1007\/s11882-015-0511-7","article-title":"Neural abnormalities in nonallergic rhinitis","volume":"15","author":"Bernstein","year":"2015","journal-title":"Curr Allergy Asthma Rep"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2017.05.008","article-title":"Brainstem mechanisms underlying the cough reflex and its regulation","volume":"243","author":"Mutolo","year":"2017","journal-title":"Respir Physiol Neurobiol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.08.026","article-title":"Capsaicin treatment reduces nasal hyperreactivity and transient receptor potential cation channel subfamily V, receptor 1 (TRPV1) overexpression in patients with idiopathic rhinitis","volume":"133","author":"Van Gerven","year":"2014","journal-title":"J Allergy Clin Immunol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1111\/all.15060","article-title":"Self-reported nasal hyperreactivity is common in all chronic upper airway inflammatory phenotypes and not related to general well-being","volume":"76","author":"Backaert","year":"2021","journal-title":"Allergy"},{"key":"B20","doi-asserted-by":"publisher","first-page":"100132","DOI":"10.1016\/j.waojou.2020.100132","article-title":"Prevalence and triggers of self-reported nasal hyperreactivity in adults with asthma","volume":"13","author":"Feijen","year":"2020","journal-title":"World Allergy Organ J"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1002\/lary.23495","article-title":"Short-time cold dry air exposure: A useful diagnostic tool for nasal hyperresponsiveness","volume":"122","author":"Van Gerven","year":"2012","journal-title":"Laryngoscope"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2020.09.024","article-title":"Less is more: rare pulmonary neuroendocrine cells function as critical sensors in lung","volume":"55","author":"Xu","year":"2020","journal-title":"Dev Cell"},{"key":"B23","doi-asserted-by":"publisher","first-page":"eaan8546","DOI":"10.1126\/science.aan8546","article-title":"Pulmonary neuroendocrine cells amplify allergic asthma responses","volume":"360","author":"Sui","year":"2018","journal-title":"Science"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.05.034","article-title":"Enterochromaffin cells are gut chemosensors that couple to sensory neural pathways","volume":"170","author":"Bellono","year":"2017","journal-title":"Cell"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2016.00564","article-title":"Mechanosensory signaling in enterochromaffin cells and 5-HT release: potential implications for gut inflammation","volume":"10","author":"Linan-Rico","year":"2016","journal-title":"Front Neurosci"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01778-2015","article-title":"Neuro-immune interactions in chemical-induced airway hyperreactivity","volume":"48","author":"Devos","year":"2016","journal-title":"Eur Respir J"},{"key":"B27","doi-asserted-by":"crossref","DOI":"10.4324\/9781315152837-15","article-title":"Roles of neuronal TRP channels in neuroimmune interactions","volume-title":"Neurobiology of TRP Channels 2nd ed","author":"L\u00f3pez-Requena","year":"2017"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1053\/prrv.2000.0126","article-title":"Pulmonary neuroendocrine cells (PNEC) and neuroepithelial bodies (NEB): chemoreceptors and regulators of lung development","volume":"2","author":"Lommel","year":"2001","journal-title":"Paediatr Respir Rev"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/S0034-5687(99)00018-3","article-title":"Neuroepithelial bodies as airway oxygen sensors","volume":"115","author":"Cutz","year":"1999","journal-title":"Respir Physiol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad7969","article-title":"Pulmonary neuroendocrine cells function as airway sensors to control lung immune response","volume":"351","author":"Branchfield","year":"2016","journal-title":"Science"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.12.029","article-title":"Identification of enteroendocrine regulators by real-time single-cell differentiation mapping","volume":"176","author":"Gehart","year":"2019","journal-title":"Cell"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1002\/iub.2218","article-title":"Chromogranin A in the early steps of the neurosecretory pathway","volume":"72","author":"Laguerre","year":"2020","journal-title":"Int Union Biochem Mol Biol Life"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.06.081","article-title":"ASCL1 and NEUROD1 reveal heterogeneity in pulmonary neuroendocrine tumors and regulate distinct genetic programs","volume":"16","author":"Borromeo","year":"2016","journal-title":"Cell Rep"},{"key":"B34","doi-asserted-by":"publisher","first-page":"109011","DOI":"10.1016\/j.celrep.2021.109011","article-title":"Airway basal stem cells generate distinct subpopulations of PNECs","volume":"35","author":"Mou","year":"2021","journal-title":"Cell Rep"},{"key":"B35","doi-asserted-by":"publisher","first-page":"101083","DOI":"10.1016\/j.isci.2020.101083","article-title":"Efficient generation and transcriptomic profiling of human iPSC-derived pulmonary neuroendocrine cells","volume":"23","author":"Hor","year":"2020","journal-title":"iScience"},{"key":"B36","article-title":"Command-line tools for processing biological sequencing data","author":"Aronesty","year":"2011","journal-title":"Ea-Utils"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.2174\/1875036201307010001","article-title":"Comparison of sequencing utility programs","author":"Aronesty","year":"2013","journal-title":"Ea-Utils"},{"key":"B38","volume-title":"FASTQC. A quality control tool for high throughput sequence data","author":"Andrews","year":"2010"},{"key":"B39","volume-title":"10x Genomics Cell Ranger 4.0.0 using 10x Genomics Cloud Analysis","year":"2020"},{"key":"B40","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2015","journal-title":"Genome Biol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.05.031","article-title":"Comprehensive integration of single-cell data","volume":"177","author":"Stuart","year":"2019","journal-title":"Cell"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1101\/2023.10.30.563174","article-title":"CZ CELLxGENE Discover: A single-cell data platform for scalable exploration, analysis and modeling of aggregated data","author":"CZI","year":"2023","journal-title":"bioRxiv"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1","DOI":"10.5114\/aoms.2016.57577","article-title":"Chromogranin A \u2013 unspecific neuroendocrine marker. Clinical utility and potential diagnostic pitfalls","volume":"12","author":"Gut","year":"2016","journal-title":"Arch Med Sci"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1007\/s12022-022-09708-2","article-title":"Overview of the 2022 WHO classification of neuroendocrine neoplasms","volume":"33","author":"Rindi","year":"2022","journal-title":"Endocr Pathol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1038\/nature24489","article-title":"A single-cell survey of the small intestinal epithelium","volume":"551","author":"Harber","year":"2017","journal-title":"Nature"},{"key":"B46","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1038\/s41467-021-27901-5","article-title":"Robust differentiation of human enteroendocrine cells from intestinal stem cells","volume":"13","author":"Zeve","year":"2022","journal-title":"Nat Commun"},{"key":"B47","article-title":"Constitutive achaete-scute homologue-1 promotes airway dysplasia and lung neuroendocrine tumors in transgenic mice","volume":"60","author":"Linnoila","year":"2000","journal-title":"Cancer Res"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1242\/dev.127.18.3913","article-title":"Basic helix-loop-helix transcription factors regulate the neuroendocrine differentiation of fetal mouse pulmonary epithelium","volume":"127","author":"Ito","year":"2000","journal-title":"Development"},{"key":"B49","doi-asserted-by":"publisher","first-page":"e78216","DOI":"10.7554\/eLife.78216","article-title":"Neuroendocrinology of the lung revealed by single-cell RNA sequencing. Noble PW, Shen M, editors","volume":"11","author":"Kuo","year":"2022","journal-title":"eLife"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1038\/nature23676","article-title":"The neuropeptide neuromedin U stimulates innate lymphoid cells and type 2 inflammation","volume":"549","author":"Klose","year":"2017","journal-title":"Nature"},{"key":"B51","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/S0165-1838(97)00030-1","article-title":"Postnatal development of the pulmonary neuroepithelial bodies in various animal species","volume":"65","author":"Van Lommel","year":"1997","journal-title":"J Auton Nerv Syst"},{"key":"B52","article-title":"Mapping the distribution of neuroepithelial bodies of the rat lung. A whole-mount immunohistochemical approach","volume":"150","author":"Avadhanam","year":"1997","journal-title":"Am J Pathol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.11.058","article-title":"Directed migration of pulmonary neuroendocrine cells toward airway branches organizes the stereotypic location of neuroepithelial bodies","volume":"13","author":"Noguchi","year":"2015","journal-title":"Cell Rep"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64728-1","article-title":"Alteration of Pulmonary Neuroendocrine Cells during Epithelial Repair of Naphthalene-Induced Airway Injury Author links open overlay panel","volume":"156","author":"Peake","year":"2000","journal-title":"Am J Pathol"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1126\/science.aba0629","article-title":"Airway stem cells sense hypoxia and differentiate into protective solitary neuroendocrine cells","volume":"371","author":"Shivaraju","year":"2021","journal-title":"Science"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00755.2003","article-title":"Oxygen sensing: applications in humans","volume":"96","author":"Cherniack","year":"1985","journal-title":"J Appl Physiol"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1038\/365153a0","article-title":"Oxygen sensing in airway chemoreceptors","volume":"365","author":"Youngson","year":"1993","journal-title":"Nature"},{"key":"B58","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1152\/physiol.00045.2008","article-title":"Regulation of oxygen homeostasis by hypoxia-inducible factor 1","volume":"24","author":"Semenza","year":"2009","journal-title":"Physiol Bethesda"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1007\/978-94-007-4584-1_21","article-title":"Hyperplasia of pulmonary neuroepithelial bodies (NEB) in lungs of prolyl hydroxylase -1(PHD-1) deficient mice","volume":"758","author":"Pan","year":"2012","journal-title":"Adv Exp Med Biol"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2008.05.006","article-title":"Expression of nicotinic receptors in normal and tumoral pulmonary neuroendocrine cells (PNEC)","volume":"204","author":"Sartelet","year":"2008","journal-title":"Pathol  Res Pract"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1038\/nature20793","article-title":"Piezo2 senses airway stretch and mediates lung inflation-induced apnoea","volume":"541","author":"Nonomura","year":"2017","journal-title":"Nature"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2012-0068OC","article-title":"Neuroepithelial bodies as mechanotransducers in the intrapulmonary airway epithelium involvement of TRPC5","volume":"47","author":"Lembrechts","year":"2012","journal-title":"Am J Respir Cell Mol Biol"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00167.2005","article-title":"Mechanical stretch-induced serotonin release from pulmonary neuroendocrine cells: implications for lung development","volume":"290","author":"Pan","year":"2006","journal-title":"Am J Physiol-Lung Cell Mol Physiol"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2022.08.010","article-title":"Pulmonary neuroendocrine cells sense succinate to stimulate myoepithelial cell contraction","volume":"57","author":"Yu","year":"2022","journal-title":"Dev Cell"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.10.014","article-title":"Interleukin-33 promotes serotonin release from enterochromaffin cells for intestinal homeostasis","volume":"54","author":"Chen","year":"2021","journal-title":"Immunity"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.2500\/ajr.2008.22.3211","article-title":"Computational fluid dynamics simulation of airflow in the normal nasal cavity and paranasal sinuses","volume":"22","author":"Xiong","year":"2008","journal-title":"Am J Rhinol Allergy"},{"key":"B67","doi-asserted-by":"publisher","first-page":"2485","DOI":"10.1038\/s41467-020-16239-z","article-title":"Dissecting the cellular specificity of smoking effects and reconstructing lineages in the human airway epithelium","volume":"11","author":"Goldfarbmuren","year":"2020","journal-title":"Nat Commun"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2013-0199OC","article-title":"Chemosensory functions for pulmonary neuroendocrine cells","volume":"50","author":"Gu","year":"2014","journal-title":"Am J Respir Cell Mol Biol"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.2174\/157339808785161314","article-title":"Pulmonary neuroendocrine cell system in health and disease","volume":"4","author":"Cutz","year":"2008","journal-title":"Curr Respir Med Rev"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1378\/chest.10-1304","article-title":"Neuroendocrine cell distribution and frequency distinguish neuroendocrine cell hyperplasia of infancy from other pulmonary disorders","volume":"139","author":"Young","year":"2011","journal-title":"Chest"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.20243","article-title":"Persistent tachypnea of infancy is associated with neuroendocrine cell hyperplasia","volume":"40","author":"Deterding","year":"2005","journal-title":"Pediatr Pulmonol"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2022.5631","article-title":"Emerging strategies for the treatment of small cell lung cancer: A review","volume":"9","author":"Petty","year":"2023","journal-title":"JAMA Oncol"},{"key":"B73","doi-asserted-by":"publisher","first-page":"820","DOI":"10.3390\/cancers13040820","article-title":"Pathology and classification of SCLC","volume":"13","author":"Raso","year":"2021","journal-title":"Cancers"},{"key":"B74","doi-asserted-by":"publisher","first-page":"69","DOI":"10.2147\/HP.S103957","article-title":"Hyperplasia and hypertrophy of pulmonary neuroepithelial bodies, presumed airway hypoxia sensors, in hypoxia inducible factor prolyl hydroxylase deficient mice","volume":"4","author":"Pan","year":"2016","journal-title":"Hypoxia"},{"key":"B75","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1016\/j.cell.2015.09.021","article-title":"Formation of a neurosensory organ by epithelial cell slithering","volume":"163","author":"Kuo","year":"2015","journal-title":"Cell"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1394539\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T04:23:44Z","timestamp":1723004624000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1394539\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,7]]},"references-count":75,"alternative-id":["10.3389\/fimmu.2024.1394539"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2024.1394539","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,7]]},"article-number":"1394539"}}