title: Vitamin D deficiency induces Th2 skewing and eosinophilia in neonatal allergic airways disease.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Leukocyte Biology Section, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: J E
authors.initials: JE
authors.lastname: Vasiliou
authors.forename: S
authors.initials: S
authors.lastname: Lui
authors.forename: S A
authors.initials: SA
authors.lastname: Walker
authors.forename: V
authors.initials: V
authors.lastname: Chohan
authors.forename: E
authors.initials: E
authors.lastname: Xystrakis
authors.forename: A
authors.initials: A
authors.lastname: Bush
authors.forename: C M
authors.initials: CM
authors.lastname: Hawrylowicz
authors.forename: S
authors.initials: S
authors.lastname: Saglani
authors.forename: C M
authors.initials: CM
authors.lastname: Lloyd
mesh_terms: D056151:Airway Remodeling; D000818:Animals; D000831:Animals, Newborn; D001249:Asthma / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006967:Hypersensitivity / Q000276:immunology*; D008168:Lung / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011657:Pulmonary Eosinophilia / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014808:Vitamin D Deficiency / Q000276:immunology*
keywords: animal models; asthma; eosinophils; lymphocytes; paediatric