Benzo[a]pyrene Aggravates Psoriasis-Like Skin Inflammation via Circulating Exosomal microRNA Modulation

Benzo[a]pyrene (BaP), a polycyclic aromatic hydrocarbon and environmental pollutant, has been implicated in the exacerbation of psoriasis, although the underlying molecular mechanisms remain unclear. In this study, we investigated the role of BaP in inflammation, focusing on serum exosomes, using a mouse model of imiquimod (IMQ)-induced psoriasis. Topical BaP exposure aggravated psoriatic skin inflammation and increased the expression of aryl hydrocarbon receptor (AhR), CYP1A1, and proinflammatory cytokines in lesional skin. Serum exosomes from BaP + IMQ-treated mice enhanced cytokine expression in primary mouse keratinocytes. High-throughput miRNA profiling revealed that 81 and 91 miRNAs were upregulated in serum exosomes from IMQ- and BaP + IMQ-treated mice, respectively, compared to controls. Notably, mmu-miR-423-3p was the most upregulated in both groups, as validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Consistently, hsa-miR-423-5p was significantly elevated in circulating exosomes from psoriasis patients compared to healthy controls, confirmed by miRNA sequencing and qRT-PCR. KEGG pathway analysis linked hsa-miR-423-5p to the MAPK signalling pathway. Functionally, miR-423-5p triggered an increase in the expression of pro-inflammatory cytokines and oxidative stress in psoriatic keratinocytes. These findings suggest that BaP exacerbates psoriatic inflammation via AhR signalling and that serum exosomal miR-423 may serve as a biomarker for environmentally induced psoriasis exacerbation.