MedElevator
Войти в исследования Frontiers in immunology · 2025
Benzo[a]pyrene exacerbates allergen-induced airway inflammation through NLRP3-dependent dendritic cell activation and pathogenic T helper cell polarization.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Zou Huamei, Duan Jiaqi, Xie Yongmin, Chen Ruien, Ye Yanyu, Zhang Aizhi, Yang Pingchang, Yang Gui, Liu Xiaoyu
Аннотация
BACKGROUND: 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.
OBJECTIVE: We investigated how BaP co-exposure modifies house dust mite (HDM)-driven allergic airway responses, focusing on the role of the NLRP3 inflammasome in dendritic cells (DCs).
METHODS: 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-/- mice, in vitro bone marrow-derived DC (BMDC) cultures, and adoptive transfer of lung DCs. T helper cell polarization was analyzed in OT-II co-culture assays.
RESULTS: 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-/- mice, which failed to produce IL-1β/IL-18 and exhibited attenuated inflammation. In vitro, BaP synergized with HDM to activate NLRP3 in BMDCs, leading to caspase-1 cleavage, IL-1β release, and enhanced CD80/CD86 expression. Adoptive transfer of BaP/HDM-exposed WT lung DCs, but not Nlrp3-/- DCs, was sufficient to drive allergic airway inflammation in naïve recipients. Finally, BaP-conditioned WT DCs skewed naïve CD4+ T cells toward Th2 and Th17 lineages, an effect absent in Nlrp3-/- DCs.
CONCLUSION: 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.
OBJECTIVE: We investigated how BaP co-exposure modifies house dust mite (HDM)-driven allergic airway responses, focusing on the role of the NLRP3 inflammasome in dendritic cells (DCs).
METHODS: 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-/- mice, in vitro bone marrow-derived DC (BMDC) cultures, and adoptive transfer of lung DCs. T helper cell polarization was analyzed in OT-II co-culture assays.
RESULTS: 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-/- mice, which failed to produce IL-1β/IL-18 and exhibited attenuated inflammation. In vitro, BaP synergized with HDM to activate NLRP3 in BMDCs, leading to caspase-1 cleavage, IL-1β release, and enhanced CD80/CD86 expression. Adoptive transfer of BaP/HDM-exposed WT lung DCs, but not Nlrp3-/- DCs, was sufficient to drive allergic airway inflammation in naïve recipients. Finally, BaP-conditioned WT DCs skewed naïve CD4+ T cells toward Th2 and Th17 lineages, an effect absent in Nlrp3-/- DCs.
CONCLUSION: 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.