{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T06:18:56Z","timestamp":1783491536827,"version":"3.55.0"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"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. Allergy"],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Mugwort (\n                      <jats:italic>Artemisia vulgaris<\/jats:italic>\n                      ) is a predominant aeroallergen for allergic rhinitis (AR) in northern China. However, the molecular changes linking local nasal mucosal inflammation with systemic alterations remain incompletely understood. This study aimed to explore the cross-level regulatory network in a mouse model of mugwort-induced AR by combining nasal mucosal transcriptomics and serum metabolomics.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      BALB\/c mice were sensitized with mugwort extract and then challenged intranasally to establish an AR model. Nasal mucosal tissues were collected for RNA sequencing, and serum samples from the same cohort were subjected to non-targeted metabolomic analysis. Transcription factor (TF)-associated analysis, pathway enrichment analysis, and integrative multi-omics analysis were used to identify candidate regulatory factors and pathways involved in mugwort-induced allergic inflammation. Targeted validation of arginine-related changes was performed by measuring serum Arg1 and L-arginine levels, followed by\n                      <jats:italic>ARG2<\/jats:italic>\n                      knockdown analysis in BEAS-2B epithelial cells after mugwort extract stimulation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Transcriptomic analysis revealed a clear Th2-type immune response in the model group, with significant upregulation of\n                      <jats:italic>Il13<\/jats:italic>\n                      ,\n                      <jats:italic>Arg1<\/jats:italic>\n                      ,\n                      <jats:italic>Ccl24<\/jats:italic>\n                      and\n                      <jats:italic>Il6<\/jats:italic>\n                      . In addition, many downregulated genes were enriched in pathways related to ciliary function and epithelial differentiation, accompanied by suppression of structural genes such as\n                      <jats:italic>Krt25<\/jats:italic>\n                      and\n                      <jats:italic>Krt71<\/jats:italic>\n                      . Gene set enrichment and TF-associated analyses further highlighted cytokine-mediated signaling and potential upstream regulators, including\n                      <jats:italic>Fos<\/jats:italic>\n                      ,\n                      <jats:italic>Batf<\/jats:italic>\n                      , and\n                      <jats:italic>Mafb<\/jats:italic>\n                      . Serum metabolomics showed increased 1-methylhistamine and enrichment of arachidonic acid metabolism in mugwort-treated mice. Integrated analysis of the two omics datasets further pointed to arginine-related metabolism as a shared altered pathway. Consistently, targeted assays showed increased serum Arg1 levels and decreased serum L-arginine concentrations in the mugwort group. In BEAS-2B cells,\n                      <jats:italic>ARG2<\/jats:italic>\n                      knockdown attenuated the induction of\n                      <jats:italic>IL6<\/jats:italic>\n                      and\n                      <jats:italic>CCL26<\/jats:italic>\n                      after mugwort extract stimulation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Together, our findings indicate that mugwort-induced AR is accompanied by coordinated local and systemic changes, including immune activation, epithelial\/ciliary dysfunction, and serum metabolic remodeling. The arginine-related alterations supported by both omics analysis and targeted validation provide a potential link between nasal mucosal inflammation and systemic metabolic changes in mugwort allergy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/falgy.2026.1835987","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:58:14Z","timestamp":1783490294000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Artemisia pollen-induced allergic rhinitis in mice: multi-omics dissection of local and systemic molecular alterations"],"prefix":"10.3389","volume":"7","author":[{"given":"Jiaoni","family":"Chi","sequence":"first","affiliation":[{"name":"Department of Allergy, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College","place":["Beijing, China"]},{"name":"Research Unit of New Techniques for Live-cell Metabolic Imaging, Chinese Academy of Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Allergy, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxuan","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Allergy, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Lyu","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Allergy, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajie","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Trauma-Emergency & Critical Care Medicine, Shanghai Fifth People\u2019s Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1124","DOI":"10.1111\/all.70153","article-title":"Long-term effect of allergen immunotherapy in responder local allergic rhinitis patients: symptom control, and prevention of asthma and allergic sensitizations","volume":"81","author":"Testera-Montes","year":"2026","journal-title":"Allergy"},{"key":"B2","doi-asserted-by":"publisher","first-page":"3069","DOI":"10.1111\/all.14586","article-title":"Advances and novel developments in allergic rhinitis","volume":"75","author":"Meng","year":"2020","journal-title":"Allergy"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1787","DOI":"10.1111\/all.70072","article-title":"Efficacy of house dust Mite immunotherapy in Chinese allergic rhinitis patients with diverse sensitization patterns: a multicenter study (COVER study)","volume":"81","author":"Xu","year":"2026","journal-title":"Allergy"},{"key":"B4","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1001\/jama.2024.0530","article-title":"Allergic rhinitis","volume":"331","author":"Bernstein","year":"2024","journal-title":"JAMA"},{"key":"B5","doi-asserted-by":"publisher","first-page":"2163","DOI":"10.1111\/all.15223","article-title":"The prevalence of non-allergic rhinitis phenotypes in the general population: a cross-sectional study","volume":"77","author":"Avdeeva","year":"2022","journal-title":"Allergy"},{"key":"B6","doi-asserted-by":"publisher","first-page":"100744","DOI":"10.1016\/j.waojou.2023.100744","article-title":"Prevalence and risk factors of allergic rhinitis among Chinese adults: a nationwide representative cross-sectional study","volume":"16","author":"Zhang","year":"2023","journal-title":"World Allergy Organ J"},{"key":"B7","doi-asserted-by":"publisher","first-page":"179426","DOI":"10.1155\/2015\/179426","article-title":"Artemisia allergy research in China","volume":"2015","author":"Tang","year":"2015","journal-title":"Biomed Res Int"},{"key":"B8","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1111\/all.13597","article-title":"Artemisia pollen allergy in China: component-resolved diagnosis reveals allergic asthma patients have significant multiple allergen sensitization","volume":"74","author":"Gao","year":"2019","journal-title":"Allergy"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1652915","DOI":"10.3389\/fmicb.2025.1652915","article-title":"Integrated gut microbiome and metabolomics analysis reveals microbial-metabolic cross-talk in allergic rhinitis","volume":"16","author":"Sun","year":"2025","journal-title":"Front Microbiol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"894","DOI":"10.1111\/all.16001","article-title":"Differential modulation of allergic rhinitis nasal transcriptome by dupilumab and allergy immunotherapy","volume":"79","author":"Wipperman","year":"2024","journal-title":"Allergy"},{"key":"B11","doi-asserted-by":"publisher","first-page":"406","DOI":"10.3390\/metabo13030406","article-title":"Multi-Omics analysis of lung tissue demonstrates changes to lipid metabolism during allergic sensitization in mice","volume":"13","author":"Turi","year":"2023","journal-title":"Metabolites"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1555664","DOI":"10.3389\/fimmu.2025.1555664","article-title":"Distinct metabolomic signatures in allergic rhinitis with concurrent chronic spontaneous urticaria: an untargeted metabolomics analysis reveals novel biomarkers and pathway alterations","volume":"16","author":"Lyu","year":"2025","journal-title":"Front Immunol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"771136","DOI":"10.3389\/fimmu.2021.771136","article-title":"Airway microbiome and Serum metabolomics analysis identify differential candidate biomarkers in allergic rhinitis","volume":"12","author":"Yuan","year":"2022","journal-title":"Front Immunol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/j.jaci.2012.02.013","article-title":"A critical role of IL-33 in experimental allergic rhinitis","volume":"130","author":"Haenuki","year":"2012","journal-title":"J Allergy Clin Immunol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1111\/cea.12597","article-title":"Diesel exhaust particles exacerbate allergic rhinitis in mice by disrupting the nasal epithelial barrier","volume":"46","author":"Fukuoka","year":"2016","journal-title":"Clin Exp Allergy"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1550205","DOI":"10.3389\/fgene.2025.1550205","article-title":"Bioinformatics analysis combined with untargeted metabolomics reveals lipid metabolism-related genes and their biological markers in chronic spontaneous urticaria","volume":"16","author":"Hu","year":"2025","journal-title":"Front Genet"},{"key":"B17","doi-asserted-by":"publisher","first-page":"50538","DOI":"10.3791\/50538","article-title":"An effective manual deboning method to prepare intact mouse nasal tissue with preserved anatomical organization","volume":"78","author":"Dunston","year":"2013","journal-title":"J Vis Exp"},{"key":"B18","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1038\/s41392-020-00443-w","article-title":"Metabolism pathways of arachidonic acids: mechanisms and potential therapeutic targets","volume":"6","author":"Wang","year":"2021","journal-title":"Signal Transduct Target Ther"},{"key":"B19","doi-asserted-by":"publisher","first-page":"e363","DOI":"10.1002\/mco2.363","article-title":"Arachidonic acid metabolism in health and disease","volume":"4","author":"Zhang","year":"2020","journal-title":"MedComm"},{"key":"B20","doi-asserted-by":"publisher","first-page":"2682","DOI":"10.1016\/j.ajpath.2011.02.041","article-title":"Characterization of the cysteinyl leukotriene 2 receptor in novel expression sites of the gastrointestinal tract","volume":"178","author":"Barajas-Espinosa","year":"2011","journal-title":"Am J Pathol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"S52","DOI":"10.1164\/ajrccm\/143.3_Pt_2.S52","article-title":"Airway luminal liquid: sources and role as an amplifier of bronchoconstriction","volume":"143","author":"Yager","year":"1991","journal-title":"Am Rev Respir Dis"},{"key":"B22","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1089\/ars.2018.7627","article-title":"Bioenergetic differences in the airway epithelium of lean Versus obese asthmatics are driven by nitric oxide and reflected in circulating platelets","volume":"31","author":"Winnica","year":"2019","journal-title":"Antioxid Redox Signal"},{"key":"B23","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1165\/rcmb.2010-0041OC","article-title":"Simvastatin improves epithelial dysfunction and airway hyperresponsiveness","volume":"44","author":"Ahmad","year":"2011","journal-title":"Am J Respir Cell Mol Biol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"2465","DOI":"10.1172\/JCI82925","article-title":"Increased mitochondrial arginine metabolism supports bioenergetics in asthma. Journal of clinical investigation","volume":"126","author":"Xu","year":"2016","journal-title":"J Clin Invest"},{"key":"B25","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1183\/09031936.05.00010805","article-title":"dsRNA enhances eotaxin-3 production through interleukin-4 receptor upregulation in airway epithelial cells","volume":"26","author":"Tsuji","year":"2005","journal-title":"Eur Respir J"},{"key":"B26","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1016\/j.jaci.2016.07.020","article-title":"Proton pump inhibitors decrease eotaxin-3\/CCL26 expression in patients with chronic rhinosinusitis with nasal polyps: possible role of the nongastric H,K-ATPase","volume":"139","author":"Min","year":"2017","journal-title":"J Allergy Clin Immunol"}],"container-title":["Frontiers in Allergy"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/falgy.2026.1835987\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:58:15Z","timestamp":1783490295000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/falgy.2026.1835987\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,8]]},"references-count":26,"alternative-id":["10.3389\/falgy.2026.1835987"],"URL":"https:\/\/doi.org\/10.3389\/falgy.2026.1835987","relation":{},"ISSN":["2673-6101"],"issn-type":[{"value":"2673-6101","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,8]]},"article-number":"1835987"}}