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

Abstract

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 6 weeks, 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.

Identification of genes differentially regulated by vitamin D deficiency that alter lung pathophysiology and inflammation in allergic airways disease

“…Vitamin D has important immunomodulatory properties, as evidenced by the widespread expression of the vitamin D receptor on immune cells, including activated T and B cells, macrophages, and dendritic cells (18). Studies have shown that vitamin D deficiency can exacerbate allergic airways inflammation (39). Thus, in addition to its potential role in airway remodeling and the development of AHR (11) (discussed below), vitamin D deficiency may promote asthma symptoms by skewing the immune response toward a Th2 phenotype.…”

“…Our laboratory has recently shown that in utero vitamin D deficiency increases airway smooth muscle (ASM) mass and AHR in mice and differentially regulates genes involved in embryonic lung development (39). Data suggest that the structural alterations that are observed in the lungs of asthmatic patients may have origins in early life (25), and, as such, vitamin D may also contribute to asthma pathogenesis by influencing lung development.…”

Serum Immunoglobulin E and Vitamin D3 in Bronchial Asthma

“…The findings of vitamin D 3 deficiency and serum IgE of present study is in agreement with other previous studies. [22][23][24] Vitamin D 3 levels of <20 ng/ml were noted in 78.66% of bronchial asthma patients [22] and a positive association was noted with severity of clinical symptoms. Other studies [23,24] noted vitamin D 3 deficiency in 67% and 91% of patients respectively, the findings support the observations of present study.…”

“…[22][23][24] Vitamin D 3 levels of <20 ng/ml were noted in 78.66% of bronchial asthma patients [22] and a positive association was noted with severity of clinical symptoms. Other studies [23,24] noted vitamin D 3 deficiency in 67% and 91% of patients respectively, the findings support the observations of present study. Ginde [25] and Eman [26] had reported severe vitamin D 3 deficiency in bronchial asthma.…”

“…In present study, the vitamin D 3 deficiency was noted with elevated serum IgE levels, the findings are highly consistent with previous studies. [25,26] Previous studies [23][24][25][26] found elevated serum IgE level and vitamin D 3 deficiency in bronchial asthma. In the light of above literature review and evidence based findings of present study, it is suggested the vitamin D 3 supplements may improve the health of bronchial asthma patients.…”