Benzo a pyrene exacerbates allergen-induced airway inflammation through
NLRP3-dependent dendritic cell activation and pathogenic T helper cell
polarization
#MMPMID41346596
Zou H
; Duan J
; Xie Y
; Chen R
; Ye Y
; Zhang A
; Yang P
; Yang G
; Liu X
Front Immunol
2025[]; 16
(?): 1699886
PMID41346596
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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-1?/IL-18 and
exhibited attenuated inflammation. In vitro, BaP synergized with HDM to activate
NLRP3 in BMDCs, leading to caspase-1 cleavage, IL-1? 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.
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