Project Details

Description

The objective of this proposal is to define molecular and cellular targets of vitamin D in the immune system. There is a large body of anecdotal data to suggest that there is a link between vitamin D status and the human autoimmune disease multiple sclerosis. Experimentally, vitamin D deficiency exacerbates experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Furthermore supplementation of mice with vitamin D can suppress and prevent symptoms of EAE. Two targets of vitamin D in the immune system have been identified the interleukin (IL)-4. secreting type-2 helper T (Th2) cells and transforming growth factor (TGF)-beta1 (two cytokines shown to be protective in EAE) secreting cells. The hypotheses to be tested are: 1. Vitamin D status regulates Th cell differentiation. 2. Vitamin D treatment of EAE results because of the induction of Th2 cells. 3. Vitamin D induction of Th2 cells and protection from EAE depends on TGF-beta1 synthesis. 4. Vitamin D negatively regulates Th1 effector cells. Th cell differentiation and function will be measured as a function of increasing vitamin D both in vitro and in vivo in Th cells from T cell receptor transgenic mice. T cells from vitamin D treated mice will be isolated and tested for their ability to transfer protection from EAE. TGF-beta1 will be neutralized in vitro and in vivo to determine if vitamin D functions via the transcriptional upregulation of TGF-beta1. Similarly, TGF-beta1 supplementation will be done and compared to vitamin D treatment for the mechanisms by which they suppress EAE. Th2 cell deficient mice will be used as a source of Th1 effector cells and vitamin D will be tested as a direct regulator of Th1 function. A better understanding of how vitamin D effectively blocks EAE is necessary for proper nutritional counseling and optimal treatment of multiple sclerosis patients.
StatusFinished
Effective start/end date1/5/0112/31/03

Funding

  • National Institute of Neurological Disorders and Stroke: $204,739.00
  • National Institute of Neurological Disorders and Stroke: $207,460.00
  • National Institute of Neurological Disorders and Stroke: $231,651.00
  • National Institute of Neurological Disorders and Stroke: $207,355.00

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