Reversible Control by Vitamin D of Granulocytes and Bacteria in the Lungs of Mice: An Ovalbumin-Induced Model of Allergic Airway Disease

Abstract

Vitamin D may be essential for restricting the development and severity of allergic diseases and asthma, but a direct causal link between vitamin D deficiency and asthma has yet to be established. We have developed a ‘low dose’ model of allergic airway disease induced by intraperitoneal injection with ovalbumin (1 µg) and aluminium hydroxide (0.2 mg) in which characteristics of atopic asthma are recapitulated, including airway hyperresponsiveness, antigen-specific immunoglobulin type-E and lung inflammation. We assessed the effects of vitamin D deficiency throughout life (from conception until adulthood) on the severity of ovalbumin-induced allergic airway disease in vitamin D-replete and -deficient BALB/c mice using this model. Vitamin D had protective effects such that deficiency significantly enhanced eosinophil and neutrophil numbers in the bronchoalveolar lavage fluid of male but not female mice. Vitamin D also suppressed the proliferation and T helper cell type-2 cytokine-secreting capacity of airway-draining lymph node cells from both male and female mice. Supplementation of initially vitamin D-deficient mice with vitamin D for four weeks returned serum 25-hydroxyvitamin D to levels observed in initially vitamin D-replete mice, and also suppressed eosinophil and neutrophil numbers in the bronchoalveolar lavage fluid of male mice. Using generic 16 S rRNA primers, increased bacterial levels were detected in the lungs of initially vitamin D-deficient male mice, which were also reduced by vitamin D supplementation. These results indicate that vitamin D controls granulocyte levels in the bronchoalveolar lavage fluid in an allergen-sensitive manner, and may contribute towards the severity of asthma in a gender-specific fashion through regulation of respiratory bacteria.

Vitamin D Deficiency and the Lung: Disease Initiator or Disease Modifier?

“…The authors went on to investigate whether these effects were dependent on the timing of vitamin D treatment, and found that eosinophil recruitment was inhibited when 1,25(OH) 2 D was administered at a later stage in the exposure protocol. This work is supported by Gorman and colleagues [52] who showed that vitamin D deficiency in a mouse model of OVA exposure suppresses allergic responses in a sex dependent manner. Interestingly, the apparent sensitivity of male mice to the effects of vitamin D deficiency was associated with an increase in bacteria levels in the lung implying a role for vitamin D induced modulation of the microbiome in regulating asthma like responses in the airway.…”

The Role of Vitamin D in the Immune System as a Pro-survival Molecule

“…182 An inhibitory effect from 1α,25(OH) 2 D 3 vitamin or calcitriol has been reported also for eosinophils. 102,183 This would highlight the role of vitamin D in asthma. 184,185 In children with asthma, an impaired T-reg population with an altered cytokine spectrum and an increase in CD23 þ CD21 þ -expressing B cells has recently been observed.…”

The genomic origins of asthma

“…In this study it was not possible to distinguish the effects of maternal vitamin D status versus the role of the vitamin D status of the individual after birth on lung development. 72 A recent publication by our group further explored the mechanisms for explaining the association of vitamin D, lung development and asthma. 73 Previously we investigated the overlap between genes related to vitamin D relative to different DLCGS to infer the role of in utero changes of vitamin D responsive genes in the developing lung and asthma.…”