VITAMIN D REGULATION OF TYPE-2 HELPER T CELL RESPONSES

Project: Research project

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 date1/5/0112/31/01

Funding

  • National Institute of Neurological Disorders and Stroke: $231,651.00

Fingerprint

Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.