Polystyrene particles induces asthma-like Th2-mediated lung injury through IL-33 secretion.

Plastics, particularly polystyrene (PS), are extensively used worldwide, especially in disposable packaging, which contributes to environmental pollution by generating microplastic particles. Herein, we investigated the pulmonary toxic effects of PS microplastics, focusing on airway inflammation and immune response. PS microplastic (50 nm to 1 μm) exposure was more likely to cause a severe pulmonary inflammatory response, particularly with smaller particle sizes. PS microplastic nose-only inhalation led to pulmonary toxic effects, which is specifically focusing on airborne microplastic exposure via inhalation in humans. We demonstrated that PS microplastic exposure in mice led to significant asthma-like symptoms, including airway inflammation, airway hyperresponsiveness, bronchial epithelial mucus cell hyperplasia, and Th2 immune responses through the IL-33 signalling pathway. Additionally, spatial transcriptome analysis indicated that epithelial cells drive the IL-33 signalling pathway and Th2 cell activation within PS-induced lung injury. PS-stimulated primary epithelial cells with the conditioned medium treatment in C57BL/6 mouse-derived splenocytes increased the Th2 immune response, including cytokine levels and mRNA expression. Meanwhile, Th2-mediated lung inflammation induced by PS exposure was effectively regulated by an IL-33 inhibitor or dexamethasone treatment. These findings enhance our understanding of the toxicological implications of microplastic exposure in the respiratory system and assist in developing potential mitigation strategies.