{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:22:20Z","timestamp":1792002140898,"version":"4.4.0"},"reference-count":63,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T00:00:00Z","timestamp":1749513600000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003395","name":"Shanghai Municipal Education Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003395","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Pulmonary neuroendocrine cells (PNECs) are adjacent to the vagus nerve, which innervates the lungs, and have been implicated in asthma pathogenesis. However, the neuroimmunomodulatory role of vagal\u2010PNEC signaling in asthma remains poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We developed an asthma model of C\u2010fiber photoactivation and vagotomy to investigate the changes in PNECs. RNA sequencing (RNA\u2010seq) was performed on flow cytometry\u2010sorted PNECs to explore how vagus nerve C fibers affect the function of PNECs, with further validation in an in\u00a0vitro cell model. Single\u2010nucleus RNA sequencing (snRNA\u2010seq) was conducted on airway samples of patients before and after bronchial thermoplasty (BT) treatment, and the changes of neural signals in different airway cell types and their crosstalk with PNEC after BT were analyzed in depth.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Vagotomy reduced photoactivated TRPA1\u2010mediated PNEC activation and allergic inflammation, inhibited the number and function of PNEC, and attenuated PNEC\u2010mediated asthma response. PNEC RNA\u2010seq results showed that photoactivation of TRPA1 in lung could promote the migration, aggregation, and synaptic transmission of PNECs and increase the synthesis and secretion of neuropeptides, which could also be activated by \u03b17 nAChR of PNECs. BT therapy significantly reduced or interrupted NRG1\u2010ERBB signaling between PNECs and other cells by interfering with PNEC secretion, synapse formation, and signaling, thereby alleviating the condition of asthma patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We found that the vagal TRPA1\u2010PNEC axis contributes to asthma severity. BT can disrupt this pathway through NRG1\u2010ERBB signaling between PNECs and other cells to attenuate the inflammatory response in asthma.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/all.16599","type":"journal-article","created":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T03:19:36Z","timestamp":1749525576000},"page":"1715-1736","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Disruption of the Vagal\n                    <scp>TRPA1<\/scp>\n                    \u2010Pulmonary Neuroendocrine Cell Axis Reduces Asthma Severity"],"prefix":"10.1111","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2945-0593","authenticated-orcid":false,"given":"Xintong","family":"Feng","sequence":"first","affiliation":[{"name":"Department of Respiratory Endoscopy, Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Department of Respiratory and 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Endoscopy, Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Shanghai Engineering Research Center of Respiratory Endoscopy  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Respiratory Endoscopy, Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Shanghai Engineering Research Center of Respiratory Endoscopy  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangfang","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of 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