Vitamin D insufficiency/deficiency is widespread in asthma, and epidemiological studies point to an association between low serum 25-hydroxyvitamin D level and poor asthma control and increased severity. In humans, vitamin D is principally derived from sunlight induced cutaneous conversion of 7-dehydrocholesterol to vitamin D and oral supplementation. We sought to determine if established and chronic-persistent adult asthma patients from a South-Florida pulmonary patient population, with abundant sunshine availability and oral vitamin D supplementation exhibit vitamin D insufficiency/deficiency. A trend to vitamin D insufficiency was observed in approximately 65% of both adult asthma patients and apparently healthy (non-asthmatic) volunteers. Among asthma patients, serum 25-hydroxyvitamin D levels positively correlated with the control of their disease as ascertained by a questionnaire.
The role of vitamin D in regulating highly inflammatory Th9 memory lymphocytes in adult chronic human asthma is largely unknown. To this end, purified memory T cells from the blood of adult asthmatics were polarized to the Th9 phenotype using cytokines mimicking those found in the chronic asthmatic lung fluids and stimulated/expanded non-specifically with anti-CD3, anti-CD28 monoclonal antibodies. Following the Th9 polarization protocol adult asthmatics exhibited a higher percentage of IL-9+ memory T-cells compared to healthy controls. Both storage and active forms of vitamin D decreased the percentage of cells positive for IL-9, as well as those positive for other cytokines/chemokine IL-5, IL-8, and IL-17. The transcription factors required for Th9 conversion, PU.1 and IRF-4, were down-regulated by vitamin D. The generation of Th9 cells was inhibited equally by vitamin D and dexamethasone when used alone, but the effect was additive when both steroids were used in combination.
Our studies using non-specifically stimulated cells were extended by analyzing the effect of vitamin D on allergen specific stimulation. The response of CD4+ T cells obtained from the blood of house dust mite positive asthmatics was studied. House dust mite allergen elicited a classical Th2 phenotype response (IL-4, IL-5, IL-9, and IL-13 cytokine profile) and vitamin D effectively inhibited those key Th2 cytokines.
We conclude that vitamin D appears to be of significant clinical benefit in our cohort of patients, i.e., established chronic adult human asthma, by down-regulating key immune cells including Th9, Th17, and Th2 involved in this disorder.
|Advisor:||Hartmann, James X.|
|Commitee:||Houri-Shirazi, Mahyar, Iragavarapu, Vijaya L., Mari, Frank|
|School:||Florida Atlantic University|
|School Location:||United States -- Florida|
|Source:||DAI-B 74/11(E), Dissertation Abstracts International|
|Subjects:||Nutrition, Physiology, Immunology|
|Keywords:||Asthma, Dehydrocholesterol, Memory T cells, Serum 25-hydroxyvitamin D, Vitamin D insufficiency|
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