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Vitamin D deficiency induces T h2 skewing and eosinophilia in neonatal allergic airways disease
Author(s) -
Vasiliou J. E.,
Lui S.,
Walker S. A.,
Chohan V.,
Xystrakis E.,
Bush A.,
Hawrylowicz C. M.,
Saglani S.,
Lloyd C. M.
Publication year - 2014
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.12465
Subject(s) - vitamin d deficiency , vitamin d and neurology , medicine , immunology , eosinophilia , allergic inflammation , offspring , endocrinology , vitamin , inflammation , vitamin a deficiency , house dust mite , allergy , pregnancy , biology , allergen , retinol , genetics
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 CD 3 + CD 4 + T1 ST 2 + cells and reduced CD 4 + 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.