Vitamin D deficiency induces Th2 skewing and eosinophilia in neonatal allergic airways disease

Autor: J E, Vasiliou, S, Lui, S A, Walker, V, Chohan, E, Xystrakis, A, Bush, C M, Hawrylowicz, S, Saglani, C M, Lloyd
Rok vydání: 2014
Předmět:
Zdroj: Allergy
ISSN: 1398-9995
Popis: 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.
Databáze: OpenAIRE
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