{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T23:08:28Z","timestamp":1773702508865,"version":"3.50.1"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T00:00:00Z","timestamp":1763510400000},"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":"\n Background<\/jats:title>\n Environmental pollutants are known to aggravate allergic diseases, but the molecular mechanisms by which polycyclic aromatic hydrocarbons such as benzo[a]pyrene (BaP) potentiate allergic airway inflammation remain poorly understood.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n We investigated how BaP co-exposure modifies house dust mite (HDM)\u2013driven allergic airway responses, focusing on the role of the NLRP3 inflammasome in dendritic cells (DCs).<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Mice were sensitized and challenged intranasally with HDM with or without BaP. Airway hyperresponsiveness (AHR), bronchoalveolar lavage (BAL) cell counts, lung histopathology, and serum HDM-specific IgE were assessed. Cytokine production and epithelial alarmins were measured by ELISA. The role of NLRP3 was evaluated using Nlrp3\n \u2212<\/jats:sup>\n \/\n \u2212<\/jats:sup>\n mice,\n in vitro<\/jats:italic>\n bone marrow\u2013derived DC (BMDC) cultures, and adoptive transfer of lung DCs. T helper cell polarization was analyzed in OT-II co-culture assays.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Co-exposure to BaP and HDM markedly exacerbated airway inflammation, with enhanced AHR, increased eosinophil and neutrophil infiltration, severe goblet cell hyperplasia, and elevated HDM-specific IgE. Cytokine analysis revealed synergistic induction of Th2 (IL-4, IL-5, IL-13) and Th17 (IL-17A) responses, alongside increased epithelial alarmins (TSLP, IL-33). This exacerbated phenotype was abolished in Nlrp3\n \u2212<\/jats:sup>\n \/\n \u2212<\/jats:sup>\n mice, which failed to produce IL-1\u03b2\/IL-18 and exhibited attenuated inflammation.\n In vitro<\/jats:italic>\n , BaP synergized with HDM to activate NLRP3 in BMDCs, leading to caspase-1 cleavage, IL-1\u03b2 release, and enhanced CD80\/CD86 expression. Adoptive transfer of BaP\/HDM-exposed WT lung DCs, but not Nlrp3\n \u2212<\/jats:sup>\n \/\n \u2212<\/jats:sup>\n DCs, was sufficient to drive allergic airway inflammation in na\u00efve recipients. Finally, BaP\u2013conditioned WT DCs skewed na\u00efve CD4\n +<\/jats:sup>\n T cells toward Th2 and Th17 lineages, an effect absent in Nlrp3\n \u2212<\/jats:sup>\n \/\n \u2212<\/jats:sup>\n DCs.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n BaP amplifies allergic airway disease by activating the NLRP3 inflammasome in DCs, thereby enhancing DC maturation, cytokine release, and pathogenic Th2\/Th17 polarization. These findings identify a critical mechanism linking environmental pollutants to exacerbated allergic asthma and highlight the NLRP3 inflammasome as a potential therapeutic target.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1699886","type":"journal-article","created":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T06:36:28Z","timestamp":1763534188000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Benzo[a]pyrene exacerbates allergen-induced airway inflammation through NLRP3-dependent dendritic cell activation and pathogenic T helper cell 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