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RATIONALE Little is known about vitamin D status and its effect on asthma pathophysiology in children with severe, therapy-resistant asthma (STRA). OBJECTIVES Relationships between serum vitamin D, lung function, and pathology were investigated in pediatric STRA. METHODS Serum 25-hydroxyvitamin D [25(OH)D(3)] was measured in 86 children (mean age, 11.7(More)
We show that a combination of the immunosuppressive drugs, vitamin D3 and Dexamethasone, induced human and mouse naive CD4(+) T cells to differentiate in vitro into regulatory T cells. In contrast to the previously described in vitro derived CD4(+) T cells, these cells produced only interleukin (IL)-10, but no IL-5 and interferon (IFN)-gamma, and(More)
The mode of action of Leflunomide, an immunomodulatory drug used in rheumatoid arthritis, is debated. This study, using 14C-labeled de novo purine and pyrimidine synthesis precursors, proves conclusively that the prime target in proliferating human T-lymphocytes is pyrimidine biosynthesis at the level of dihydroorotic-acid dehydrogenase. Leflunomide (25 and(More)
IMPORTANCE Asthma and wheezing begin early in life, and prenatal vitamin D deficiency has been variably associated with these disorders in offspring. OBJECTIVE To determine whether prenatal vitamin D (cholecalciferol) supplementation can prevent asthma or recurrent wheeze in early childhood. DESIGN, SETTING, AND PARTICIPANTS The Vitamin D Antenatal(More)
We previously reported that human CD4+ Tregs secrete high levels of IL-10 when stimulated in the presence of dexamethasone and calcitriol (vitamin D3). We now show that following stimulation by allergen, IL-10-secreting Tregs inhibit cytokine secretion by allergen-specific Th2 cells in an IL-10-dependent manner. A proportion of patients with severe asthma(More)
SUMMARY Interleukin-10 (IL-10) is a cytokine with broad anti-inflammatory properties by its suppression of both macrophage and dendritic cell function, including antigen-presenting cell function and the production of proinflammatory cytokines. This can result subsequently in the feedback regulation of both T-helper 1 (Th1)-type and Th2-type responses. This(More)
Regulatory T cells are proposed to play a central role in the maintenance of immunological tolerance in the periphery, and studies in many animal models demonstrate their capacity to inhibit inflammatory pathologies in vivo. At a recent meeting [Clinical Application of Regulatory T Cells, 7-8 April 2005, Horsham, UK, organized by the authors of this review,(More)
Recent studies suggest that human regulatory T (T reg) cells protect against the development of allergic and asthmatic disease and that their function is impaired during active disease. Two new studies contribute to our understanding of the role that T reg cells play in the control of allergic airway disease in mice. However, these studies also highlight(More)
Recent studies from several laboratories have shown that the concentrations of anti-immunoglobulin antibodies required to induce B lymphocytes to synthesize DNA are quite different from those needed to activate these cells, i.e. to cause resting B cells to leave G0. The present experiments examine this difference in detail. Thus, stimulation of DNA(More)