Journal
ALLERGY
Volume 69, Issue 10, Pages 1380-1389Publisher
WILEY-BLACKWELL
DOI: 10.1111/all.12465
Keywords
animal models; asthma; eosinophils; lymphocytes; paediatric
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Funding
- Wellcome Trust, UK [083526/Z/07/Z]
- [86718/Z/08/Z]
- Asthma UK [AUK-AC-2012-01, MRC-AsthmaUKCentre, 10/058] Funding Source: researchfish
- Medical Research Council [G1000758B, G1000758] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0510-10192] Funding Source: researchfish
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BackgroundAssociations 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). MethodsIn 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 6weeks, when airway hyper-responsiveness (AHR), airway inflammation and remodelling were assessed. ResultsNeonatal 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. ConclusionPeri-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.
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