Network toxicological and single-cell sequencing reveals the potential mechanisms of psoriatic toxicity of polybrominated diphenyl ethers.

Polybrominated diphenyl ethers (PBDEs), major brominated flame retardants, have been implicated in various health issues due to their environmental persistence and bioaccumulation. PBDEs preferentially accumulate in the skin due to their low hydrophobicity and may contribute to the onset of psoriasis. In this study, we aimed to investigate the potential mechanisms of PBDE-induced psoriatic toxicity by utilizing network toxicology at single-cell resolution. Initially, 139 overlapping targets between PBDEs and psoriasis were identified, and their protein-protein interactions (PPIs) were mapped. Enrichment analysis indicated that PBDEs-targeted genes might worsen psoriatic lesions through an overactive immune response. Single-cell sequencing revealed a comprehensive immune cell activation, predominantly through the IL-24 signaling pathway, in response to PBDE enrichment. Moreover, the molecular docking analysis revealed that PBDEs exhibited specific binding interactions with hub targets such as HSP90AA1, MAPK3, MMP9, TP53, and CASP3, which are crucial for psoriasis pathogenesis. In conclusion, our findings establish a solid theoretical basis for understanding the potential molecular mechanisms underlying PBDE-induced cutaneous toxicity. Integrating network toxicology with single-cell sequencing refines the prediction accuracy of pollutant exposure across pathogenic mechanisms. This study presents an interdisciplinary strategy with untapped potential for mitigating pollutant exposure, thereby aiding in the prevention and treatment of related diseases.