Dietary Modulation of Immune Function and Oxidative Stress
Immunity and Disease Prevention Research Unit
Project Number: 2032-51530-018-00
Start Date: Jan 18, 2009
End Date: Jan 17, 2014
Objective 1: Conduct a controlled, vitamin D supplementation trial in volunteers with vitamin D insufficiency (VDI) to determine if supplementation to achieve the proposed level of >75 nmol/L for maintenance of bone health is also appropriate for maintenance of immune function. Sub-objective 1A. Determine if supplements decrease the production of proinflammatory and increase the production of anti-inflammatory cytokines and chemokines by innate immune cells stimulated ex vivo. Objective 1B. Determine if supplements decrease serum markers of inflammation and autoimmune activity, and increase serum levels of defensive molecules. Objective 1C. Determine if supplements decrease blood levels of proinflammatory T-helper type 1 (Th1) and Th17 cells and increase levels of anti-inflammatory T-regulatory (Treg) and Th2 cells.
Objective 2: Determine the impact of plant polyphenols and polyphenol-rich foods on immune cell function using cell culture systems, mouse models, and human volunteers. Examine anti-inflammatory and anti-cancer activities of polyphenols in animal models, as well as inflammation and oxidative damage in studies with human volunteers, including overweight/obese individuals. Objective 2A. Analyze the effects of polyphenol-rich foods and individual plant polyphenols on immune cell function in vivo and ex vivo. Ojective 2B. Examine anti-inflammatory activities of polyphenol-rich foods, individual plant polyphenols and vitamin A in mice and humans who are at risk for developing inflammatory disease, such as autoimmune mice and obese humans. Objective 2C. Evaluate the anti-cancer activity of polyphenol-rich foods and individual plant polyphenols.
Objective 3: Examine the absorption of B-cryptoxanthin (CX) from supplements and foods, its contribution to vitamin A stores, and the impact of CX, other carotenoids and vitamin A on immune function. Objective 3A. Measure the absorption and metabolism of CX from Satsuma mandarin juice fed to healthy adult humans. Objective 3B. Estimate the impact of daily consumption of food sources of CX or B-carotene (BC) on plasma and breast milk concentrations of CX, BC and retinol in lactating women. Objective 3C. Determine the impact of CX on immune and bone marker status in the Mongolian gerbil.
Objective 4: Determine if high-level vitamin A intake is associated with higher Th2 and Treg responses and lower Th1 and Th17 responses relative to adequate and deficient intake. Objective 4A. Using dietary and targeted gene disruption approaches in mice, determine if vitamin A enhances Th2 and Treg responses by acting directly on T cells. Objective 4B. Using subjects recruited in the vitamin D supplementation trial described under Objective 1, determine if vitamin A status is associated with higher blood levels of NK, NK-T, Th2 and Treg cells, and lower levels of Th1 and Th17 cells.
Objective 5: Identify the role of dietary selenium and selenoproteins in regulating cellular responses to oxidative stress. Objective 5A. Identify the pro-inflammatory and anti-inflammatory proteins S-glutathionylated by selenoprotein W. Objective 5B. Determine the role of selenoprotein W in key inflammatory pathways.
The impact of selenium, vitamins A and D, and plant polyphenols, on immune function will be examined using cell culture systems, mouse models, and human intervention trials. The anti-cancer activities of polyphenols will be examined in animal models. Absorption of beta-cryptoxanthin will be examined in gerbils and humans. The effect of selenium on cell division and cell signaling will be examined in cell culture.