Flavor chemicals in vaping products induce pulmonary dendritic cell maturation

Vaping products contain numerous flavor chemicals that are known immunological sensitizers associated with the elicitation of immune-mediated hypersensitivity responses. Therefore, we investigated the immune response associated with sensitizing flavor chemicals in vaping liquids and focused on dendritic cell maturation as it is a crucial early cellular event of the sensitization immunological cascade. Bone marrow-derived dendritic cells (BMDDCs) were used to assess induction of dendritic cell maturation upon treatment with unique flavor vaping liquids and aerosol condensates. Female BALB/c mice were exposed 2 h/day for 4 days to nicotine-free vaping aerosols containing a mixture of citral, cinnamaldehyde, dihydrocoumarin, and vanillin. In vitro experiments indicate that cinnamaldehyde and citral, but not vaping liquid solvents, dihydrocoumarin and vanillin, are capable of inducing BMDDC maturation. In vivo, we observed an increase in the expression of maturation marker MHC class II (MHCII) on conventional dendritic cells (cDCs) in the lung tissue of mice exposed to flavored vaping aerosols compared with exposure controls. Maturation was specifically observed on CD11b+ cDCs and not CD103+ cDCs. No significant changes were observed for macrophages, neutrophils, B and T lymphocytes in the lung tissue, and bronchoalveolar lavage. Also, we found that regulatory T lymphocytes had decreased expression of CD25 in mice exposed to flavored vaping aerosols compared with exposure controls. These findings indicate that flavored chemicals can lead to rapid dendritic cell maturation in vitro and in vivo, representing an early cellular event related to respiratory sensitization and pulmonary disease.<b>NEW & NOTEWORTHY</b> Current research on vaping do not report major impact on cellular immune response. However, our findings support that flavored vaping aerosol exposure can lead to rapid modulation of dendritic cells and regulatory T lymphocytes in the lungs and extrapulmonary location. Although our findings were obtained in acute settings, they entertain the possibility that chronic exposure to vaping aerosols could progressively trigger the immunological cascade responsible for the development of serious lung diseases resembling hypersensitivity pneumonitis.