RATIONALE: Children who are vitamin D deficient are uniquely susceptible to the effects of traffic-related air pollution (TRAP) exposure. Thus we hypothesized that vitamin D deficiency increases susceptibility to DEP exacerbated allergic asthma and this effect can be mitigated with Vitamin D supplementation.
METHODS: Using established mouse models of asthma, we examined the impact of pre-and post-natal vitamin D supplementation on asthma development as well as the utility of vitamin D as a treatment for established asthma in the context of diesel-exhaust particle (DEP) exposure.
RESULTS: DEP and allergen co-exposure resulted in increased airway hyperresponsiveness (AHR) and accumulation of pathogenic Th2/Th17 cells in the lungs of vitamin D deficient mice compared to control mice. Prenatal and postnatal vitamin D supplementation significantly attenuated the development of AHR, and decreased pulmonary accumulation of Th2/Th17 cells following co-exposure to TRAP and allergen, but not allergen alone. Restoration of normal vitamin D status had no impact on AHR once asthma was already established.
CONCLUSIONS: Our data establish that vitamin D confers protection against asthma development specifically in the context of TRAP exposure. While vitamin D replacement did not reverse established asthma, restoration of normal vitamin D status in early life significantly attenuated the development of AHR in DEP-exacerbated allergic asthma and reduced lung Th2/Th17 cells, which portend the development of severe asthma.