Dietary Modulation of Immune Function and Oxidative Stress
Immunity and Disease Prevention Research Unit
Project Number: 5306-51530-020-00
Start Date: Jan 18, 2014
End Date: Sep 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. Objective 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.