Background: Fine particulate matter (PM_2.5) exposure significantly exacerbates respiratory morbidity, particularly in asthmatic individuals, highlighting an urgent need for effective therapeutic interventions. In this study, we evaluated the therapeutic potential and underlying mechanisms of human dental pulp stem cells (hDPSCs), a promising mesenchymal stem cell population, in mitigating airway inflammation in mice with PM_2.5-induced asthma exacerbation.

Methods: In a PM_2.5-exacerbated ovalbumin (OVA)-asthma murine model, hDPSCs were intravenously administered with MCC950 (NLRP3 inhibitor) as positive control, systematically evaluating their therapeutic effects on airway inflammation and pyroptosis through pulmonary function tests, histopathological examination, cytological and molecular analyses.

Results: The administration of hDPSCs ameliorated airway inflammation. Moreover, hDPSCs further alleviated Th2 inflammation and decreased serum IgE concentrations, along with a decrease in eosinophils in BALF. At the same time, interleukin-1β (IL-1β) and IL-18 levels in BALF and caspase-1 activity in lung tissues were reduced. In addition, immunohistochemistry showed that the expression levels of NLRP3, caspase-1, GSDMD, cleaved capsase-1 and IL-1β were reduced. The western blot results also showed that the expression level of NLRP3/caspase-1/GSDMD/cleaved capsase-1 in the classical pathway of pyroptosis decreased after hDPSCs intervention.

Conclusions: These findings provided the first evidence that hDPSCs transplantation attenuated allergic airway inflammation and mucus secretion in mice with PM_2.5-induced asthma exacerbation. Thus, hDPSCs exert these protective effects through suppression of the NLRP3/caspase-1/GSDMD-mediated pyroptosis pathway, suggesting their potential as a novel cell-based therapy for PM_2.5 inhalation-mediated asthma.