{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:36:50Z","timestamp":1787567810413,"version":"build-2736575974"},"reference-count":64,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01AI153331"],"award-info":[{"award-number":["1R01AI153331"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI141642"],"award-info":[{"award-number":["R01AI141642"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82371126"],"award-info":[{"award-number":["82371126"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82371127"],"award-info":[{"award-number":["82371127"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82301289"],"award-info":[{"award-number":["82301289"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Allergic rhinitis (AR) is a common airway disease characterized by epithelial barrier dysfunction and Type 2 inflammation. Although the aryl hydrocarbon receptor (AhR) regulates mucosal immunity and epithelial homeostasis, its role in epithelial pathology in AR remains poorly defined. We sought to determine the contribution of AhR signaling to AR pathogenesis and to identify downstream mechanisms linking barrier dysfunction to Type 2 inflammation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      AhR expression and transcriptomic profiles were analyzed in nasal tissues from AR patients and controls. AhR\u2010deficient (\n                      <jats:italic>AhR<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>\u2010\/\u2010<\/jats:italic>\n                      <\/jats:sup>\n                      ) mice and\n                      <jats:italic>CC10\u2010CreER<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>TM<\/jats:italic>\n                      <\/jats:sup>\n                      ;\n                      <jats:italic>p16<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>f\/f<\/jats:italic>\n                      <\/jats:sup>\n                      (\n                      <jats:italic>p16<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>cKO<\/jats:italic>\n                      <\/jats:sup>\n                      ) mice were used to assess the contributions of AhR signaling and p16\u2010dependent epithelial senescence\u2010associated programs to allergic inflammation and barrier integrity. Mechanistic pathways were interrogated using transcriptomic analysis, and pharmacologic modulation was evaluated by molecular docking and functional assays.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      AhR expression was significantly increased in nasal epithelial cells from AR patients.\n                      <jats:italic>AhR<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>\u2010\/\u2010<\/jats:italic>\n                      <\/jats:sup>\n                      AR mice exhibited reduced Type 2 inflammation and preservation of epithelial barrier integrity. Transcriptomic analysis revealed enrichment of senescence\u2010associated signatures in AR epithelium. AhR deficiency in primary epithelial cultures and\n                      <jats:italic>AhR<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>\u2010\/\u2010<\/jats:italic>\n                      <\/jats:sup>\n                      mice markedly attenuated epithelial senescence\u2010associated programs. Consistently,\n                      <jats:italic>p16<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>cKO<\/jats:italic>\n                      <\/jats:sup>\n                      AR mice showed reduced allergic inflammation and improved barrier function. Mechanistically, NKX3\u20101 was identified as an AhR\u2010interacting regulator in cell\u2010cycle arrest. Gain\u2010 and loss\u2010of\u2010function studies demonstrated that NKX3\u20101 contributes to allergen\u2010induced epithelial senescence\u2010associated programs. Finally, curcumin attenuated epithelial senescence\u2010associated phenotypes with concomitant suppression of AhR and NKX3\u20101 expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings support a context\u2010dependent model in which AhR\u2013NKX3\u20101\u2010associated epithelial senescence programs contribute to barrier dysfunction and allergic inflammation in AR.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/all.70489","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T09:45:22Z","timestamp":1787564722000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Epithelial\n                    <scp>AhR<\/scp>\n                    \u2013\n                    <scp>NKX3<\/scp>\n                    \u20101\u2013Senescence Axis Drives Barrier Function and Inflammation in Allergic Rhinitis"],"prefix":"10.1111","author":[{"given":"Xuan","family":"Yuan","sequence":"first","affiliation":[{"name":"Division of Allergy and Clinical Immunology Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Department of Otolaryngology Head and Neck Surgery Xiangya Hospital of Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixiang","family":"Zeng","sequence":"additional","affiliation":[{"name":"Division of Allergy and Clinical Immunology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaobing","family":"Xie","sequence":"additional","affiliation":[{"name":"Division of Allergy and Clinical Immunology Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Department of Otolaryngology Head and Neck Surgery Xiangya Hospital of Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery Xiangya Hospital of Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Gu","sequence":"additional","affiliation":[{"name":"Division of Allergy and Clinical Immunology Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Department of Respiratory Medicine Children's Hospital of Soochow University  Suzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minxuan","family":"Hu","sequence":"additional","affiliation":[{"name":"Division of Allergy and Clinical Immunology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery Xiangya Hospital of Central South University  Changsha Hunan China"},{"name":"Hunan Province Key Laboratory of Otolaryngology Critical Diseases Xiangya Hospital of Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angel","family":"Xu","sequence":"additional","affiliation":[{"name":"Division of Allergy and Clinical Immunology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3854-8923","authenticated-orcid":false,"given":"Weihong","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery Xiangya Hospital of Central South University  Changsha Hunan China"},{"name":"Hunan Province Key Laboratory of Otolaryngology Critical Diseases Xiangya Hospital of Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihai","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery Xiangya Hospital of Central South University  Changsha Hunan China"},{"name":"Hunan Province Key Laboratory of Otolaryngology Critical Diseases Xiangya Hospital of Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7651-1339","authenticated-orcid":false,"given":"Peisong","family":"Gao","sequence":"additional","affiliation":[{"name":"Division of Allergy and Clinical Immunology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2024.03.023"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12016\u2010025\u201009028\u20103"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/cea.70118"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.waojou.2023.100744"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.16467"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2024.04.021"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2015.10.050"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.113972"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2025.05.012"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox15010077"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2020.04.010"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/cm9.0000000000001983"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2026.02.021"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1124\/pharmrev.122.000622"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2023.104717"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2022.04.011"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13845"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2025.102813"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14532"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/cm9.0000000000002960"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.964575"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010025\u201002500\u20108"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1421346"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.13784"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox15010022"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.23090"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.23526"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhazmat.2025.138145"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.14060"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.209296"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.Can\u201011\u20103758"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.4103\/aja.aja_44_19"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2019.12.004"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/1750\u20103841.70217"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2025.111909"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1394539"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201032552\u20101"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200904\u20100597OC"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.ado5561"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2018.10.010"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.767508"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2019.05.066"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010023\u201006287\u2010y"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21228797"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envpol.2025.127557"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573\u2010025\u201001172\u2010x"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI199952"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12016\u2010026\u201009135\u20109"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.3390\/toxics13060488"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.2500\/ajra.2016.30.4311"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2024.02.005"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhazmat.2024.135103"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envpol.2024.123674"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2023.07.016"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.30435"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adc9446"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.Can\u201004\u20102688"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159\u20108290.Cd\u201020\u20101765"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M117.793760"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23031516"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2025.08.012"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1661706"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202513645"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2025.107890"}],"container-title":["Allergy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/all.70489","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/all.70489","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/all.70489","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T09:45:23Z","timestamp":1787564723000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/all.70489"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,24]]},"references-count":64,"alternative-id":["10.1111\/all.70489"],"URL":"https:\/\/doi.org\/10.1111\/all.70489","archive":["Portico"],"relation":{},"ISSN":["0105-4538","1398-9995"],"issn-type":[{"value":"0105-4538","type":"print"},{"value":"1398-9995","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,24]]},"assertion":[{"value":"2026-02-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"all.70489"}}