Flavor chemicals in vaping products induce pulmonary dendritic cell maturation.

Abstract

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 morrow-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 2h/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 MHCII on conventional dendritic cells (cDCs) in the lung tissue of mice exposed to flavored vaping aerosols compared to 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 to 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.