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Identifying key pathophysiological determinants in airway epithelium enables novel therapeutics to prevent asthma recurrence. Here we demonstrate that TDP-43, as the master regulator of RNA metabolism, is induced in airway epithelial cells by host allergen exposure and promotes asthmatic airway responses through dampening nonsense-mediated decay (NMD) by modulating UPF1 expression, resulting in accumulation of pathogenic and NMD-sensitive transcripts including\n                    <jats:italic>CHRM1<\/jats:italic>\n                    encoding receptor that transduces the signaling of vagally-derived neurotransmitter acetylcholine. TDP-43 also facilitates airway influenza A virus replication. Intranasal application of lipid nanoparticles carrying antisense oligonucleotides targeting TDP-43 effectively reduce asthma-like pathologies in mice. Our findings indicate that targeting airway TDP-43 is therapeutically possible for asthma and influenza A virus infection-complicated asthma exacerbations.\n                  <\/jats:p>","DOI":"10.1038\/s41467-026-75901-0","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T13:18:05Z","timestamp":1784812685000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["TDP-43 promotes allergen-induced inflammation and influenza A virus replication in airway epithelium"],"prefix":"10.1038","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8508-8800","authenticated-orcid":false,"given":"Yanmei","family":"Yuan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8077-3210","authenticated-orcid":false,"given":"Wenzhu","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3539-6043","authenticated-orcid":false,"given":"Xixi","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8076-143X","authenticated-orcid":false,"given":"Chunlei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5291-2482","authenticated-orcid":false,"given":"Meiyan","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8815-9629","authenticated-orcid":false,"given":"Jian","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengpeng","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guihong","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojiang","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4059-4397","authenticated-orcid":false,"given":"Qing","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4322-1551","authenticated-orcid":false,"given":"Jun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"75901_CR1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2015.25","volume":"1","author":"ST Holgate","year":"2015","unstructured":"Holgate, S. 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