Effect of Fasting and Refeeding on T-cell Fate

Intermittent caloric restricted or fasting has numerous health effects including the reduction in numerous cardiovascular and pulmonary disease risk factors. The cellular programs activated by caloric restriction are similarly regulated in preclinical and clinical studies in response to a 24-hour fast. We have found that a beneficial effect of a 24-hour fasting blunts the activation of a component of the innate immune system, termed the NLRP3 inflammasome. This inflammasome, as a mediator of sterile inflammation, is associated with the development of diabetes, asthma and atherosclerosis. At the same time, we found that refeeding after the 24-hour fast significantly increased NLRP3 protein levels. As NLRP3 is increased in obesity, the nutrient intervention (24 hour fast and then refeeding) we studied may be useful to evaluate nutrient-overload effects on the immune system. Pertaining to this it has recently been found in a preclinical study that NLRP3 can also orchestrate differentiation of na(SqrRoot) ve T cells into T(H)2 cells. Interestingly both the NLRP3 inflammasome and T(H)2 cell activation contribute to asthma. In this context we hypothesize that the assessment of the effect on refeeding on T(H)2 cell differentiation (polarity) may allow us to dissect out the mechanisms underpinning nutrient overload induced T(H)2 cell activation. To evaluate this blood samples to test T-cell biology will be collected in subjects, at baseline, after a fixed caloric meal and in response to a 24-hour fast (water intake will not be restricted). The objective of this pilot study is to identify if nutrient-load regulates T-Cell differentiation capacity and to test whether this pathway could be investigated as a therapeutic target to blunt/negate the inflammation associated with nutrient-excess associated diseases including asthma.