Immunoregulatory mechanisms of vitamin D relevant to respiratory health and asthma

Abstract

Vitamin D deficiency is prevalent among people with various immune-mediated conditions, including autoimmune diseases and asthma. Serum 25(OH)D levels inversely correlate with asthma severity, glucocorticoid responsiveness/dosage, and markers of pathogenesis, such as airway remodeling, IgE, and eosinophilia. Trials involving supplementation with active vitamin D or a precursor are beginning to emerge with variable results that, in part, reflect differences in study design. This review looks at the mechanisms by which vitamin D may protect against asthma, including increasing glucocorticoid responsiveness, skewing immune cells towards a regulatory phenotype, reducing the incidence of infections, airway remodeling, eosinophilia, and lowering the levels of IgE. Also discussed is the therapeutic potential for vitamin D, which is likely to be applicable to immune-mediated conditions beyond simply asthma.

Vitamin D Counteracts an IL-23–Dependent IL-17A+IFN-γ+ Response Driven by Urban Particulate Matter

“…However, addition of exogenous recombinant IL-23 was unable to overcome the effect (data not shown), suggesting that 1,25(OH) 2 D 3 is also likely to act through other mechanisms to dampen Th17 responses, although there may well be redundancy in the system. Indeed, in vivo, 1,25(OH) 2 D 3 is thought to act through several immunoregulatory mechanisms to dampen Th17 responses (14). ILT3, which was shown here to be upregulated by 1,25 (OH) 2 D3 (Figure E3B), may play a role in dampening the proinflammatory response, since it has been reported to reduce the synthesis of IL-17A and IFN-g in mice (45).…”

“…Vitamin D deficiency has also been associated with the increased incidence and severity of many respiratory diseases, including asthma, as reviewed in detail elsewhere (14,18). The majority of vitamin D is generated when UV-B radiation photolyses 7-dehydrocholesterol in the skin into vitamin D 3 .…”

“…In particular, there is a substantial body of epidemiological data that detrimentally link both poor air quality and vitamin D deficiency to asthma and COPD (13,14). Exposure to elevated concentrations of ambient particulate matter (PM) has been associated with asthma exacerbations as well as increased hospitalization and medication usage, with emerging evidence supporting a role in the initiation of asthma (15).…”

“…It seems highly plausible that such effects act alongside the well-documented capacity of vitamin D to act on structural and innate cells to promote antimicrobial pathways (14). Vitamin D has…”

Pediatric Obesity-Related Asthma: The Role of Metabolic Dysregulation

“…70 Furthermore, intake of micronutrients such as vitamins A, 59, 71, 72 C, 59, 73 and E 73 has been inversely associated with asthma, whereas vitamin D insufficiency has been associated with higher asthma disease burden 74 and lower lung function. 75,76 Although the exact mechanism through which vitamin D influences asthma in obese children is not known, vitamin D does have immunomodulatory effects 77 and may influence intestinal microflora, 78 mechanisms that have been associated with asthma pathophysiology. 79,80 There is also evidence to suggest that maternal diet may influence incident childhood asthma and obesity, an aspect that has been previously reviewed.…”