Background
Associations between vitamin D status and childhood asthma are increasingly reported, but direct causation and mechanisms underlying an effect remain unknown. We investigated the effect of early‐life vitamin D deficiency on the development of murine neonatal allergic airways disease (AAD).
Methods
In utero and early‐life vitamin D deficiency was achieved using a vitamin D‐deficient diet for female mice during the third trimester of pregnancy and lactation. Offspring were weaned onto a vitamin D‐deficient or vitamin D‐replete diet, and exposure to intranasal house dust mite (HDM) or saline was commenced from day 3 of life for up to 6 weeks, when airway hyper‐responsiveness (AHR), airway inflammation and remodelling were assessed.
Results
Neonatal mice that had in utero and early‐life vitamin D deficiency had significantly increased pulmonary CD3+CD4+T1ST2+ cells and reduced CD4+IL‐10+ cells. This effect was enhanced following HDM exposure. AHR in HDM‐exposed mice was unaffected by vitamin D status. Introduction of vitamin D into the diet at weaning resulted in a significant reduction in serum IgE levels, reduced pulmonary eosinophilia and peri‐bronchiolar collagen deposition.
Conclusion
Peri‐natal vitamin D deficiency alone has immunomodulatory effects including Th2 skewing and reduced IL‐10‐secreting T regulatory cells, exaggerated with additional allergen exposure. Vitamin D deficiency in early life does not affect AHR, but contributes to disease severity with worse eosinophilic inflammation and airway remodelling. Importantly, supplementation with vitamin D improves both of these pathological abnormalities.