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首页> 外文期刊>Allergy >Vitamin D deficiency induces Th2 skewing and eosinophilia in neonatal allergic airways disease
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Vitamin D deficiency induces Th2 skewing and eosinophilia in neonatal allergic airways disease

机译：维生素D缺乏导致新生儿过敏性气道疾病的Th2偏斜和嗜酸性粒细胞增多

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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.
机译：背景：维生素D状况与儿童哮喘之间的关联越来越多，但直接的病因和作用机理尚不清楚。我们调查了早期维生素D缺乏对鼠新生儿过敏性气道疾病（AAD）的发展的影响方法：在子宫内和早期，使用维生素D缺乏饮食对雌性小鼠进行维生素D缺乏是第三次孕中期和哺乳期。将后代断奶至缺乏维生素D或富含维生素D的饮食，并从生命的第3天开始暴露于鼻内尘螨（HDM）或生理盐水，长达6周，此时气道高反应性（AHR），结果：子宫内和生命早期缺乏维生素D的新生小鼠肺CD3 + CD4 + T1ST2 +细胞明显增加，而CD4 + IL-10 +细胞减少。 HDM暴露后，这种效果得到了增强。暴露于HDM的小鼠中的AHR不受维生素D状态的影响。断奶时在饮食中添加维生素D可显着降低血清IgE水平，减少肺嗜酸性粒细胞增多和支气管周围胶原沉积。结论：围产期维生素D缺乏仅具有免疫调节作用，包括Th2偏斜和IL-10-降低。分泌的T调节细胞，并因其他过敏原暴露而被夸大。生命早期的维生素D缺乏症不会影响AHR，但会导致疾病严重程度以及嗜酸性粒细胞增多的炎症和气道重塑。重要的是，补充维生素D可以改善这两种病理异常。

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